CN102159223B

CN102159223B - Treating or preventing rotavirus infection

Info

Publication number: CN102159223B
Application number: CN2008801109127A
Authority: CN
Inventors: 米歇尔·阿夫里尔·麦康奈尔; 克莱尔·伊丽莎白·安·菲茨帕特里克; 阿拉斯代尔·凯尼斯·修·迈克基布恩; 凯瑞·特雷泽·布占; 格莱恩·斯图尔特·布占
Original assignee: Fonterra Cooperative Group Ltd
Current assignee: Fonterra Cooperative Group Ltd
Priority date: 2007-08-09
Filing date: 2008-08-08
Publication date: 2013-10-30
Anticipated expiration: 2028-08-08
Also published as: US20110300229A1; TW200916093A; RU2010108285A; CN102159223A; CN103479607A; DK2173364T3; EP2173364B1; NZ560524A; BRPI0814935A2; EP2173364A1; ES2699084T3; NZ586798A; RU2493860C2; MX2010001584A; HK1160788A1; AU2008284504A1; EP2173364A4; WO2009020405A1; CA2696035A1

Abstract

Provided is use of one or more of conjugated linoleic acid (CLA), high CLA milk fat, or one or more bovine milk lipid compositions to treat or prevent rotavirus infection.

Description

Treatment or prevention rotavirus infection

Invention field

The present invention relates to butterfat or the purposes of one or more Lac Bovis seu Bubali lipid compositions in treatment or prevention rotavirus infection of one or more conjugated linoleic acids (CLA), high CLA

Background of invention

Breast is a kind of for neonate provides important source of nutrition, nourishing biofluid.In addition, breast contains the material (agent) that is useful on immune system growth, function and keeps, and this material is essential for baby's growth.

Rotavirus is the 3rd type (dsRNA) virus of Reoviridae, and causes about 1.38 hundred million infantile diarrheas every year.95% child can suffer the outbreak of rotavirus diarrhea before five years old.In worldwide, rotavirus infection is the most general reason (Parashar et al2003) of diarrhoea hospitalization.Estimate at 1,205 child every day and die from the rotavirus disease.Because rotavirus, having one among 5 children will seek medical advice, and have a needs hospitalization among 65 children, and have a death of child among about 293 children.Death occurs in the Indian subcontinent, the Africa on the south the Sahara and South America (Parashar et al 2003) mostly.

The rotavirus particle is to be formed by 3 layers of concentric albumen.The outer field two kinds of albumen of virus, VP4 is relevant with the initial phase mutual effect of this virus and host cell with VP7.VP4 forms the projection (spikes) of extending from the virion surface, and be identified as is that virus is adhered to polypeptide, and VP7 is the calcium binding glucoprotein that forms the virion smooth surface, and be considered to relevant with the postadhesion process (Mendez et al 1999, Isa et al 2006).Entering cell is the process of a complexity, and it comprises the interaction between viral outer albumen and the cell surface molecule.In vivo, rotavirus infects by the ripe enterocyte on the intestinal villi, and external, rotavirus is attached on the various cell lines, but only has some cell lines infected.Isa et al (2006) report, virus is mixed and disorderly with the initial combination of cell surface, and subsequently interaction is the reason of cell entry cell between virus and the specificity postadhesion receptor.

Rotavirus is divided into two types based on the ability of their infection cells, and this cell processes to remove sialic acid (N-acetyl-neuraminate) residue on the host cell with neuraminidase.Rotavirus from some animal needs the sialic acid residues on the cell surface to adhere to, and comprises that many other rotavirus of Human reoviruslike agent strain do not have above-mentioned needs.These Strain are called as respectively (or not relying on sialic) Strain (Isa et al, 2006) of neuraminidase sensitivity (or relying on sialic) Strain and neuraminidase resistance.Had report to claim, sialic acid derivative can suppress animal rotavirus susceptible and not to the virus of the cell of the susceptible of Human reoviruslike agent in conjunction with (Guo et al, 1999).Had report to claim, the Ganglioside GM1 a of host cell surface in Human reoviruslike agent infects as receptor work (Guo et al, 1999).It is reported, neuraminidase is processed the neuraminidase resistance Strain with resistance can be identified and have inner sialic ganglioside (Delorme et al, 2001), this with form contrast (Isa et al, 2006) in conjunction with the neuraminidase sensitivity of the outside residue in ganglioside virus.

It is reported chemical compound lot (theaflavin, protease inhibitor, Yolk immunoglobulin, synthetic sulphation sialic acid lipid (sialyl lipid) NMSO ₃, human milk adhesion protein, MUC1 mucin and cattle macromole lactalbumin (MMWP) part) can suppress external and body in rotavirus infection, but do not have chemical compound in clinical, successfully to use (Bojsen et al, 2007; Peterson et al, 2001; Takahashi et al, 2002; Isa et al, 2006).Most of these work are to use zoosis strain rather than Human virus's strain of rotavirus to finish, for example MUC1 mucin and cattle macromole lactalbumin part (Bojsen et al 2007).Utilization is studied by the Lactalbumin concentrate that FonterraCooperative Group Limited produces, this studies show that the minimizing (Wolber et al, 2005) that has rotavirus to come off in the mouse model that utilizes rotavirus mice Strain EDIM.Kvistgaard et al, 2004 reports, Bovine Lactoferrin, Lac Bovis seu Bubali adhesion protein and cattle MUC1 mucin can not prevent vitro human Wa rotavirus infection.

The general therapeutic of rotavirus diarrhea is the rehydration therapy, but this therapy is only treated symptom, and does not treat the reason of infection.Usually do not recommend the child to use anti-diarrheal (Yung et al, 2005) yet.

Therefore, need the alternative medicine for the treatment of or prevention rotavirus infection badly.Expectation is provided for treating or prevents the alternative method of rotavirus infection or is at least the selection that the public provides usefulness.

Summary of the invention

Therefore, a first aspect of the present invention relates to one or more reagent that are used for the treatment of or prevent rotavirus infection, and this reagent is selected from:

(a) isomer of one or more conjugated linoleic acids (CLA), vaccenic acid or above-mentioned combination, or

(b) hydrolysate of the butterfat of the hydrolysate of the butterfat of the butterfat of the butterfat of high CLA, one or more high CLA part, high CLA, one or more high CLA part or above-mentioned any two or more combination,

(c) one or more butter fat compositionss, said composition is selected from

(i) butterfat, one or more butterfat part or above-mentioned combinations,

(ii) anhydrous milkfat (AMF), one or more AMF part or above-mentioned any two or more combination,

(iii) one or more are rich in the part of the butterfat of phospholipid,

(iv) one or more are rich in the part of the butterfat of ganglioside,

(v) (i) to any one or one or more multiple hydrolysates of (iv), and

(vi) (i) to any two or more combination of (v), or

(d) (a) to any two or more combination of (c).

Another aspect of the present invention relates to one or more reagent that are used for the treatment of or prevent rotavirus infection, and this reagent is selected from:

(b) hydrolysate of the butterfat part of the hydrolysate of the butterfat of the butterfat of the butterfat of high CLA, one or more high CLA part, high CLA, one or more high CLA or above-mentioned combination,

(c) (a) with (b) combination.

Another aspect of the present invention relates to and is used for the treatment of or prevents one or more reagent of rotavirus infection, and this reagent is selected from:

(i) butter fat, one or more butterfat part or above-mentioned combinations,

(ii) anhydrous butter fat (AMF), one or more AMF part or above-mentioned combinations,

(iii) one or more are rich in the part of the butter fat of phospholipid,

(iv) one or more are rich in the part of the butter fat of ganglioside,

(v) (i) to any one or one or more multiple hydrolysates of (iv), and

(vi) (i) to any two or more combination of (v).

Another aspect of the present invention relate to one or more reagent mentioned above for the preparation of the treatment or the prevention rotavirus infection compositions in purposes.

Another aspect of the present invention relates to the method for the treatment of or preventing rotavirus infection, and the method comprises to one or more reagent as indicated above of the individual effective dosage of one or more reagent as indicated above of needs.

Embodiment hereinafter can relate to any above-mentioned aspect.

In one embodiment, rotavirus is Human reoviruslike agent, namely infects people's rotavirus strain.In another embodiment, rotavirus is inhuman rotavirus strain, for example birds (for example chicken, pigeon or turkey rotavirus strain), cattle, dog, goat, horse, cat family, hare, Mus, sheep, pig or ape rotavirus strain.In one embodiment, rotavirus is neuraminidase sensitivity rotavirus.In another embodiment, rotavirus is neuraminidase resistance rotavirus.Still in another embodiment, rotavirus is the Human reoviruslike agent of neuraminidase resistance.Still in another embodiment, neuraminidase resistance Human reoviruslike agent is the strain of Wa Human reoviruslike agent.In one embodiment, individuality is the people.In one embodiment, individuality is adult, child or the baby of adult, child or baby or immunocompromised host.In another embodiment, individuality is the child of child, baby, immunocompromised host or the baby of immunocompromised host.In another embodiment, individual for being grown up, surpassing 55 years old adult, the adult of immunocompromised host, the adult above 55 years old of immunocompromised host.

In one embodiment, described reagent adheres to treat or prevent rotavirus infection by reducing virus to cell.In another embodiment, rotavirus infection is treated or prevented to described reagent by reducing the cell entry cell.In another embodiment, rotavirus infection is treated or prevented to described reagent by the virus replication that reduces in the cell.In another embodiment, described reagent packs to treat or prevent rotavirus infection by the virus that reduces in the cell.In another embodiment, rotavirus infection is treated or prevented to described reagent by the lysis that reduces virus.In one embodiment, (diarrheagenic) rotavirus infection of described reagent treatment or prevention diarrhea inducing.In another embodiment, the diarrhoea that described reagent is treated or the prevention rotavirus infection causes.

In one embodiment, the part that is rich in ganglioside comprises GD3 or GM3 or its combination.

In one embodiment, the part that is rich in phospholipid comprises one or more PHOSPHATIDYL ETHANOLAMINE, one or more phosphatidylinositols, one or more Phosphatidylserine, one or more phosphatidylcholines, one or more sphingolipids (comprise one or more sphingomyelins, one or more dihydro sphingomyelins, one or more ceramides, one or more cerebroside or one or more gangliosides or above-mentioned any two or more combination in any), one or more lysophosphatides (losing the phospholipid of a fatty acid) or above-mentioned any two or more combination in any.

In one embodiment, described reagent comprises one or more glyceride and (comprises one or more glyceryl monoacetates, one or more diglyceride, or one or more triglycerides or above-mentioned any two or more combination in any), one or more phospholipid (comprise one or more PHOSPHATIDYL ETHANOLAMINE, one or more phosphatidylinositols, one or more Phosphatidylserine, one or more phosphatidylcholines, one or more sphingolipids (as indicated above) or above-mentioned any two or more combination in any), one or more lysophosphatides (losing the phospholipid of a fatty acid), one or more ceramides, one or more ether phosphoglycerides, one or more cerebroside (comprise one or more glucosylceramides, or one or more lactosylceramides or above-mentioned combination), one or more sulfatides, or one or more gangliosides (comprise one or more monosialogangliosides, one or more bifunctional sialyltransferase gangliosides, or one or more Polysialic acid gangliosides or above-mentioned combination) or above-mentioned any two or more combination in any.

In one embodiment, described reagent is carried out administration as the composition of lipid composition.Preferred lipid composition comprises animal, plant and marine products oil ﹠ fat and the lipid that produces by microbial fermentation.Preferred Animal fat includes but not limited to fat of dairy product, and particularly butter fat comprises rare butter.

In one embodiment, described reagent is selected from rare butter, butter, butter, anhydrous milkfat (AMF) (usually by the phase reversal of rare butter or the dehydration production of butter), buttermilk, butter serum (serum), the β serum, the hard butterfat part that obtains from one or more stages of separating (comprises H, SH and SSH part), the soft butterfat part that obtains from one or more stages of separating (comprises S, SS and SSS part), the combination of hard butterfat part, the combination of soft butterfat part, hard butterfat part and the combination partly of soft butterfat, the sphingolipid part, the part that is rich in butterfat ball (or " spherical ") membrane lipid (comprises, sphingolipid for example, ceramide and cerebroside), phospholipid moiety and complex lipid part, be rich in the butterfat of CLA, be rich in butterfat part and above-mentioned any two or more the combination in any of CLA, with above-mentioned hydrolysate, and the part of described hydrolysate, and the combination of hydrolysis and/or unhydrolysed part.These parts can obtain from any derivant of full milk or colostrum and full milk or colostrum, the derivant of this full milk or colostrum comprises that the rare butter of rare butter, sour cream and milk surum is (from the butterfat matter of milk surum acquisition, comprise the clear or cheese whey of yogurt, the preferred cheese milk surum).Sour cream is from using acid-producing microorganisms, rare butter that the full milk of preferably lactic acid bacteria fermentation or colostrum obtain.

In one embodiment, butterfat or its part are selected from rare butter, butter, butter, anhydrous milkfat (AMF) (usually by the phase reversal of rare butter or the dehydration production of butter), buttermilk, the butter serum, the β serum, the hard butterfat part that obtains from one or more stages of separating (comprises H, SH and SSH part), the soft butterfat part that obtains from one or more stages of separating (comprises S, SS and SSS part), the combination of hard butterfat part, the combination of soft butterfat part, the combination of hard butterfat part and soft butterfat part and above-mentioned any two or more combination in any.

In one embodiment, AMF partly is selected from combination and above-mentioned any two or more combination in any of the combination of one or more hard butterfat parts (for example H, SH and SSH part), one or more soft butterfat parts (for example S, SS and SSS part), the combination of hard butterfat part, soft butterfat part, hard butterfat part and soft butterfat part.

In one embodiment, the part that is rich in phospholipid is selected from buttermilk, one or more buttermilk parts, butter serum, one or more butter serum parts, β serum, one or more β serum parts, one or more sphingolipid parts, one or more butterfat ball membrane lipid parts, one or more phospholipid moieties, one or more complex lipids parts and above-mentioned any two or more combination in any.

In one embodiment, the part that is rich in ganglioside is selected from the part that is rich in GD3 and GM3 and above-mentioned any two or more combination in any of the part that is rich in GM3, one or more β serums of the part that is rich in GD3, one or more β serums of buttermilk, one or more buttermilk parts, butter serum, one or more butter serum parts, β serum, one or more β serums parts, one or more β serums.

In certain embodiments, described part comprises:

(a) about 5%w/w is to the lipid of about 100%w/w, or

(b) about 40%w/w is to the lipid of about 100%w/w, or

(c) about 5%w/w is to the lipid of about 95%w/w and the about 0%w/w protein of about 75%w/w extremely, or

(d) about 15%w/w is to the lipid of about 95%w/w and the about 0%w/w protein of about 75%w/w extremely, or

(e) about 5%w/w to the lipid of about 95%w/w, about 0%w/w to the protein of about 75%w/w, about 5%w/w the phospholipid of about 85%w/w and the about 0%w/w ganglioside of about 5%w/w extremely extremely, or

(f) about 15%w/w to the lipid of about 95%w/w, about 0%w/w to the protein of about 65%w/w, about 5%w/w the phospholipid of about 70%w/w and the about 0%w/w ganglioside of about 2.5%w/w extremely extremely.

In certain embodiments, described part comprises at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or the phospholipid of 95%w/w, and (for example, about 5%w/w is to about 95%w/w can to select available scope between these are worth arbitrarily, about 10%w/w is to about 95%w/w, about 15%w/w is to about 95%w/w, about 20%w/w is to about 95%w/w, about 25%w/w is to about 95%w/w, about 30%w/w is to about 95%w/w, about 35%w/w is to about 95%w/w, about 40%w/w is to about 95%w/w, about 45%w/w is to about 95%w/w, about 50%w/w is to about 95%w/w, about 10%w/w is to about 70%w/w, about 15%w/w is to about 70%w/w, about 20%w/w is to about 70%w/w, about 25%w/w is to about 70%w/w, about 30%w/w is to about 70%w/w, about 35%w/w is to about 70%w/w, about 40%w/w is to about 70%w/w, about 45%w/w is to about 70%w/w and the phospholipid of about 50%w/w to about 70%w/w).

In certain embodiments, described part comprises at least about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29% or 30%w/w be independently selected from phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, sphingomyelins, one or more phospholipid of Phosphatidylserine and phosphatidylinositols, and (for example about 0.1%w/w is to about 30%w/w can to select available scope between these are worth arbitrarily, about 0.5%w/w is to about 30%w/w, about 1%w/w is to about 30%w/w, about 2%w/w is to about 30%w/w, about 3%w/w is to about 30%w/w, about 4%w/w is to about 30%w/w, about 5%w/w is to about 30%w/w, about 10%w/w is to about 30%w/w, about 15%w/w is to about 30%w/w, about 20%w/w is to about 30%w/w, about 0.1%w/w is to about 5%w/w, about 0.5%w/w is to about 5%w/w, about 1%w/w is to about 5%w/w, about 2%w/w is to about 5%w/w, about 3%w/w is to about 5%w/w, about 0.1%w/w is to about 10%w/w, about 0.5%w/w is to about 10%w/w, about 1%w/w is to about 10%w/w, about 2%w/w is to about 10%w/w, about 3%w/w is to about 10%w/w, about 4%w/w is to about 10%w/w, about 5%w/w is to about 10%w/w, about 6%w/w is to about 10%w/w, about 0.1%w/w is to about 20%w/w, about 0.5%w/w is to about 20%w/w, about 1%w/w is to about 20%w/w, about 2%w/w is to about 20%w/w, about 3%w/w is to about 20%w/w, about 4%w/w is to about 20%w/w, about 5%w/w is to about 20%w/w, about 10%w/w is to about 20%w/w, about 15%w/w is to the phosphatidylcholine that is independently selected from of about 20%w/w, PHOSPHATIDYL ETHANOLAMINE, sphingomyelins, one or more phospholipid of Phosphatidylserine and phosphatidylinositols).

In certain embodiments, described part comprises:

(a) about 25%w/w is to the protein of about 35%w/w, the about 15%w/w lipid of about 25%w/w and the about 5%w/w phospholipid of about 12%w/w extremely extremely, or

(b) about 25%w/w to the protein of about 35%w/w, about 15%w/w to the lipid of about 25%w/w, about 5%w/w the phospholipid of about 12%w/w, the about 5%w/w MFGM albumen of about 10%w/w and the about 0.2%w/w ganglioside of about 0.9%w/w extremely extremely extremely, or

(c) about 25%w/w to the protein of about 35%w/w, about 15%w/w to the lipid of about 25%w/w, about 5%w/w is to the phospholipid of about 12%w/w, about 1%w/w phosphatidylcholine, about 1.5%w/w PHOSPHATIDYL ETHANOLAMINE, about 1%w/w sphingomyelins, about 0.5%w/w Phosphatidylserine, the phosphatidylinositols of about 0.1%w/w to 2%w/w, the about 5%w/w MFGM albumen of about 10%w/w and the about 0.2%w/w ganglioside of about 0.9%w/w extremely extremely of about 2%w/w extremely of about 5%w/w extremely of about 6%w/w extremely of about 5%w/w extremely, or

(d) about 40%w/w is to the protein of about 60%w/w, the about 25%w/w lipid of about 45%w/w and the about 10%w/w phospholipid of about 25%w/w extremely extremely, or

(e) about 40%w/w to the protein of about 60%w/w, about 25%w/w to the lipid of about 45%w/w, about 10%w/w the phospholipid of about 25%w/w, the about 5%w/w MFGM albumen of about 20%w/w and the about 0.5%w/w ganglioside of about 2.0%w/w extremely extremely extremely, or

(f) about 46%w/w to the protein of about 52%w/w, about 28%w/w to the lipid of about 40%w/w, about 11%w/w is to the phospholipid of about 16%w/w, about 2%w/w phosphatidylcholine, about 3%w/w PHOSPHATIDYL ETHANOLAMINE, about 2.5%w/w sphingomyelins, about 0.5%w/w Phosphatidylserine, the phosphatidylinositols of about 0.5%w/w to 2%w/w, the about 5%w/w MFGM albumen of about 15%w/w and the about 0.5%w/w ganglioside of about 0.9%w/w extremely extremely of about 3%w/w extremely of about 7%w/w extremely of about 8%w/w extremely of about 6%w/w extremely, or

(g) about 50%w/w is to the protein of about 70%w/w, the about 12%w/w lipid of about 32%w/w and the about 5%w/w phospholipid of about 25%w/w extremely extremely, or

(h) about 50%w/w is to the protein of about 70%w/w, the about 12%w/w lipid of about 32%w/w extremely, about 5%w/w to the phospholipid of about 25%w/w, about 2%w/w to the phosphatidylcholine of about 8%w/w, about 2%w/w is to the PHOSPHATIDYL ETHANOLAMINE of about 10%w/w, the about 2%w/w sphingomyelins of about 8%w/w and about 1%w/w Phosphatidylserine, the about 10%w/w MFGM albumen of about 20%w/w and the about 0.5%w/w ganglioside of about 2.5%w/w extremely extremely of about 3%w/w extremely extremely, or

(i) about 56%w/w to the protein of about 65%w/w, about lipid of 18% to about 28%w/w, about 8%w/w to the phospholipid of about 20%w/w, about 2%w/w is to the phosphatidylcholine of about 8%w/w, about 2%w/w PHOSPHATIDYL ETHANOLAMINE, the about 2%w/w sphingomyelins of about 8%w/w and the about 1%w/w Phosphatidylserine of about 3%w/w and the phosphatidylinositols of about 0.5%w/w to 3%w/w, the about 10%w/w MFGM albumen of about 20%w/w and about 0.5%w/w about 2.5%w/w ganglioside extremely extremely extremely extremely of about 10%w/w extremely, or

(j) about 0%w/w is to the protein of about 10%w/w, the about 85%w/w lipid of about 97%w/w and the about 25%w/w phospholipid of about 35%w/w extremely extremely, or

(k) about 0%w/w to the protein of about 10%w/w, about 85%w/w to the lipid of about 97%w/w, about 25%w/w to the phospholipid of about 35%w/w, about 5%w/w to the phosphatidylcholine of about 10%w/w, about 7%w/w the PHOSPHATIDYL ETHANOLAMINE of about 13%w/w, about 4%w/w sphingomyelins, about 2%w/w Phosphatidylserine, about 1%w/w phosphatidylinositols, the about 0%w/w MFGM albumen of about 5%w/w and the about 1%w/w ganglioside of about 3%w/w extremely extremely of about 3%w/w extremely of about 5%w/w extremely of about 9%w/w extremely extremely, or

(l) about protein of 10% to about 15%w/w, about 80%w/w is to the lipid of about 95%w/w and the about 60%w/w phospholipid of about 80%w/w extremely, or

(m) about 10%w/w to the protein of about 15%w/w, about 80%w/w to the lipid of about 95%w/w, about 60%w/w to the phospholipid of about 80%w/w, about 10%w/w to the phosphatidylcholine of about 20%w/w, about 18%w/w the PHOSPHATIDYL ETHANOLAMINE of about 28%w/w, about 10%w/w sphingomyelins, about 4%w/w Phosphatidylserine, about 2%w/w phosphatidylinositols, the about 0%w/w MFGM albumen of about 5%w/w and the about 1%w/w ganglioside of about 5%w/w extremely extremely of about 10%w/w extremely of about 12%w/w extremely of about 20%w/w extremely extremely, or

(n) about 75%w/w is to the phospholipid of the lipid of about 99%w/w and about 15%w/w to 35%w/w, or

(o) about 80%w/w to the lipid of about 90%w/w, about 5%w/w to the phosphatidylcholine of about 15%w/w, about 5%w/w the PHOSPHATIDYL ETHANOLAMINE of about 15%w/w, the about 4%w/w sphingomyelins of about 10%w/w and about 0.1%w/w about 2%w/w Phosphatidylserine extremely extremely extremely, or

(p) about 80%w/w to the lipid of about 90%w/w, the phospholipid of about 20%w/w to 30%w/w, about 5%w/w to the phosphatidylcholine of about 15%w/w, about 5%w/w the PHOSPHATIDYL ETHANOLAMINE of about 15%w/w, about 5%w/w sphingomyelins, the about 0.5%w/w Phosphatidylserine of about 1.5%w/w and the about 0.1%w/w phosphatidylinositols of about 1.2%w/w extremely extremely of about 10%w/w extremely extremely, or

(q) about 75%w/w is to the lipid of about 95%w/w and the about 50%w/w phospholipid of about 90%w/w extremely, or

(r) about 80%w/w is to the lipid of about 90%w/w, about phosphatidylcholine of 10% to about 30%w/w, about 12%w/w PHOSPHATIDYL ETHANOLAMINE, the about 12%w/w sphingomyelins of about 22%w/w and the about 1%w/w Phosphatidylserine of about 3%w/w extremely extremely of about 22%w/w extremely, or

(s) about 75%w/w to the lipid of about 95%w/w, about 50%w/w to the phospholipid of about 90%w/w, about 10%w/w extremely PHOSPHATIDYL ETHANOLAMINE, about sphingomyelins of 12% to about 25%w/w, about 1%w/w extremely Phosphatidylserine of about 6%w/w and the phosphatidylinositols of about 0.5%w/w to 4%w/w of about 25%w/w of the phosphatidylcholine of about 45%w/w, about 12%w/w extremely, or

(t) about 80%w/w to the lipid of about 90%w/w, about 65%w/w to the phospholipid of about 75%w/w, about 10%w/w extremely PHOSPHATIDYL ETHANOLAMINE, about 12%w/w extremely sphingomyelins, about 1%w/w extremely Phosphatidylserine of about 3%w/w and the phosphatidylinositols of about 0.5%w/w to 3%w/w of about 22%w/w of about 22%w/w of the phosphatidylcholine of about 30%w/w, about 12%w/w extremely, or

(u) about 25%w/w is to the lipid of about 45%w/w and the about 0.2%w/w Ganglioside, GD3 of about 1%w/w extremely, or

(v) about 25%w/w is to the lipid of about 45%w/w, the about 10%w/w phospholipid of about 30%w/w and the about 0.2%w/w ganglioside of about 1%w/w extremely extremely, or

(w) about 25%w/w to the lipid of about 45%w/w, about 10%w/w to the phospholipid of about 30%w/w, about 2%w/w is to the phosphatidylcholine of about 5%w/w, about 3%w/w PHOSPHATIDYL ETHANOLAMINE, about 2%w/w sphingomyelins, about 2%w/w Phosphatidylserine, the about 1%w/w phosphatidylinositols of about 5%w/w and the about 0.2%w/w ganglioside of about 1%w/w extremely extremely of about 12%w/w extremely of about 5%w/w extremely of about 7%w/w extremely, or

(x) about 20%w/w is to the lipid of about 40%w/w and about 0.8%w/w about 2%w/w Ganglioside, GD3 extremely, or

(y) about 20%w/w is to the lipid of about 40%w/w, the about 5%w/w phospholipid of about 30%w/w and the about 0.8%w/w ganglioside of about 3.5%w/w extremely extremely, or

(z) about 20%w/w to the lipid of about 40%w/w, about 5%w/w to the phospholipid of about 30%w/w, about 1%w/w is to the phosphatidylcholine of about 5%w/w, about 2%w/w PHOSPHATIDYL ETHANOLAMINE, about 0.5%w/w sphingomyelins, about 1%w/w Phosphatidylserine, the about 1%w/w phosphatidylinositols of about 6%w/w and the about 0.8%w/w ganglioside of about 3.5%w/w extremely extremely of about 10%w/w extremely of about 5%w/w extremely of about 8%w/w extremely.

In one embodiment, described part comprises TL at least about 70%, the phosphatidylcholine at least about 12%, the PHOSPHATIDYL ETHANOLAMINE at least about 6%, the sphingomyelins at least about 6% and at least about 1% Phosphatidylserine.In the preferred part of this embodiment, described part comprises about 1.8% butanoic acid (4:0), about 0.3% capric acid (10:0), about 0.5% lauric acid (12:0), about 7.4% myristic acid (14:0), about 14.1% myristoleic acid (14:1), about 1.0% pentadecanoic acid (15:0), about 26.0% Palmic acid (16:0), about 1.7% palmitoleic acid (16:1), about 0.6% heptadecanoic acid (17:0), about 0.3% heptadecenoic acid (17:1), about 11.9% stearic acid (18:0), about 39.0% oleic acid (18:1), about 5.0% linoleic acid (18:2), about 2.0% linolenic acid (18:3), about 0.3% arachidic acid (20:0) and about 0.8% cholesterol.In preferred embodiments, the fatty acid of this part forms basically Phospholipid Concentrate (phospholipid concentrate) PC500 described in embodiment hereinafter ^TMPhospholipid moiety.Perhaps, described part is the hydrolysate of the part of this embodiment.

In another embodiment, described part comprises TL at least about 80%, the phosphatidylcholine at least about 30%, the PHOSPHATIDYL ETHANOLAMINE at least about 6%, the sphingomyelins at least about 15% and at least about 2% Phosphatidylserine.In the preferred part of this embodiment, described part comprises the cholesterol of about 6.6% myristic acid (14:0), about 27.0% Palmic acid (16:0), about 1.3% palmitoleic acid (16:1), about 2.3% heptadecanoic acid (17:0), about 14% stearic acid (18:0), about 38.0% oleic acid (18:1), about 6.5% linoleic acid (18:2), about 2.0% linoleic acid (18:3) and about 0.1%.In preferred embodiments, the fatty acid of this part forms the basically Phospholipid Concentrate PC600 described in embodiment hereinafter ^TMOr PC700 ^TMPhospholipid moiety.Perhaps, described part is the hydrolysate of the part of this embodiment.

In one embodiment, described part comprises TL at least about 30%, the Ganglioside, GD3 at least about 0.5% and at least about 0.4% Ganglioside GM3.In preferred embodiments, the fatty acid of this part forms the basically G500 described in example hereinafter ^TMThe ganglioside part.Perhaps, described part is hydrolysate.

In another embodiment, described part comprises TL at least about 30%, the Ganglioside, GD3 at least about 1.2% and at least about 0.2% Ganglioside GM3.In preferred embodiments, the fatty acid of this part forms basically Ganglioside (ganglioside) G600 described in example hereinafter ^TMThe ganglioside part.Perhaps, described part is the hydrolysate of this embodiment part.

In one embodiment, useful compositions comprises at least about 0.1% herein, 0.2%, 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, one or more reagent mentioned above of 99.8% or 99.9% weight ratio, perhaps useful compositions is comprised of mentioned reagent basically among the present invention, or formed by mentioned reagent, and available scope (for example, about 0.1% to about 50% can selected between these aforementioned value arbitrarily, about 0.2% to about 50%, about 0.5% to about 50%, about 1% to about 50%, about 5% to about 50%, about 10% to about 50%, about 15% to about 50%, about 20% to about 50%, about 25% to about 50%, about 30% to about 50%, about 35% to about 50%, about 40% to about 50%, about 45% to about 50%, about 0.1% to about 60%, about 0.2% to about 60%, about 0.5% to about 60%, about 1% to about 60%, about 5% to about 60%, about 10% to about 60%, about 15% to about 60%, about 20% to about 60%, about 25% to about 60%, about 30% to about 60%, about 35% to about 60%, about 40% to about 60%, about 45% to about 60%, about 0.1% to about 70%, about 0.2% to about 70%, about 0.5% to about 70%, about 1% to about 70%, about 5% to about 70%, about 10% to about 70%, about 15% to about 70%, about 20% to about 70%, about 25% to about 70%, about 30% to about 70%, about 35% to about 70%, about 40% to about 70%, about 45% to about 70%, about 0.1% to about 80%, about 0.2% to about 80%, about 0.5% to about 80%, about 1% to about 80%, about 5% to about 80%, about 10% to about 80%, about 15% to about 80%, about 20% to about 80%, about 25% to about 80%, about 30% to about 80%, about 35% to about 80%, about 40% to about 80%, about 45% to about 80%, about 0.1% to about 90%, about 0.2% to about 90%, about 0.5% to about 90%, about 1% to about 90%, about 5% to about 90%, about 10% to about 90%, about 15% to about 90%, about 20% to about 90%, about 25% to about 90%, about 30% to about 90%, about 35% to about 90%, about 40% to about 90%, about 45% to about 90%, about 0.1% to about 99%, about 0.2% to about 99%, about 0.5% to about 99%, about 1% to about 99%, about 5% to about 99%, about 10% to about 99%, about 15% to about 99%, about 20% to about 99%, about 25% to about 99%, about 30% to about 99%, about 35% to about 99%, about 40% to about 99% and about 45% to about 99%).

In one embodiment, useful compositions comprises at least about 0.001 gram herein, 0.01 gram, 0.05 gram, 0.1 gram, 0.15 gram, 0.2 gram, 0.3 gram, 0.4 gram, 0.5 gram, 1 gram, 2 grams, 3 grams, 4 grams, 5 grams, 6 grams, 7 grams, 8 grams, 9 grams, 10 grams, 11 grams, 12 grams, 13 grams, 14 grams, 15 grams, 16 grams, 17 grams, one or more reagent mentioned above of 18 grams or 19 grams, perhaps useful compositions is comprised of mentioned reagent basically among the present invention, or formed by mentioned reagent, and available scope (for example, extremely about 1 gram of about 0.01 gram can selected between these aforementioned value arbitrarily, about 0.01 gram is to about 10 grams, about 0.01 gram is to about 19 grams, about 0.1 gram is to about 1 gram, about 0.1 gram is to about 10 grams, about 0.1 gram is to about 19 grams, about 1 gram is to about 5 grams, about 1 gram is to about 10 grams, about 1 gram is to about 19 grams, about 5 grams are to about 10 grams and extremely about 19 grams of about 5 grams).

In one embodiment, useful compositions comprises about 0.1% herein, 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, the fresh whole milk of 99% or 99.9% weight ratio or newborn derivant, perhaps useful compositions is comprised of mentioned reagent basically herein, or formed by mentioned reagent, and available scope (for example, about 0.1% to about 50% can selected between these aforementioned value arbitrarily, about 0.2% to about 50%, about 0.5% to about 50%, about 1% to about 50%, about 5% to about 50%, about 10% to about 50%, about 15% to about 50%, about 20% to about 50%, about 25% to about 50%, about 30% to about 50%, about 35% to about 50%, about 40% to about 50% and about 45% to about 50%).Described newborn derivant is preferably from regeneration, powder or fresh skimmed milk, whole milk powder or the skim milk of regeneration or reduction, the skimmed milk concentrate, skimmed milk retentate (retentate), concentrated breast, ultrafiltration breast retentate, lactoprotein concentrate (MPC), lactoprotein separator (MPI), decalcification lactoprotein concentrate (MPC), low fat milk, low fat milk protein concentrate (MPC), casein, caseinate, butterfat, rare butter, butter, butter, anhydrous milkfat (AMF), buttermilk, the butter serum, the β serum, hard butterfat part, soft butterfat part, the sphingolipid part, butterfat ball membrane portions, butterfat ball membrane lipid part, phospholipid moiety, the complex lipid part, colostrum, the colostrum part, colostrum protein concentrate (CPC), colostrum whey, immunoglobulin part from colostrum, milk surum (comprises sweet whey, lactic whey, the whey powder of mineral acid milk surum or reduction), lactalbumin isolate (WPI), Lactalbumin concentrate (WPC), be derived from the compositions of any breast or colostrum processing stream (processing stream), be derived from ultrafiltration or the retentate of microfiltration acquisition or the compositions of penetrant (permeate) by any breast or colostrum processing stream, be derived from the compositions of separating penetrating of acquisition or absorbed portion by the chromatograph (including but not limited to ion and gel permeation chromatography) of any breast or colostrum processing stream, comprise and pass through multiple stage separation, difference crystallization (differential crystallisation), separated from solvent, supercritical separates, nearly critical separation, distillation, the extract of the separation preparation of centrifugalize or use modifier (such as soap or emulsifying agent) is at the extract of interior any these newborn derivants, the any hydrolysate of these derivants, the part of hydrolysate and comprise hydrolysis and/or the combination in any of any two or more these derivants in being combined in of hydrolyzable moiety not.The source that should be appreciated that these derivants can be breast or colostrum or its combination.

In one embodiment, useful compositions also comprises the medicine acceptable carrier herein.In another embodiment, described compositions for or be configured to food, beverage, food additive, beverage additive, supplementary, nutriment, medicated food, nutrition product, parenteral feed product, for meal, cosmeceutical, health product, medicine (medicament) or medicine (pharmaceutical).In one embodiment, the form of described compositions is tablet, capsule sheet (caplet), pill, hard or soft capsule or lozenge.In one embodiment, the form of described compositions is that cachet, powder, assignable powder (dispensable powder), granule, suspension, elixir, liquid maybe can join any other form in the Foods or drinks, comprise such as water breast or fruit juice.In one embodiment, described compositions also comprises one or more components (for example antioxidant), and this component avoids or reduce the degraded of described compositions in can the process after lay up period or administration.These compositionss can comprise any edible consumer goods that can carry lipid.The example of suitable edible consumer goods comprises water-based product, bakery, comprise chocolate, gel, ice cream is at interior pan work, the fruit product of reduction, snacks bar (snack bar), food bars (food bar), muesli bar (muesli bar), tablespread (spread), sauce, dip in liquid (dip), the milk product that comprises Yoghurt and cheese, comprise based on milk with based on the beverage of the beverage of non-milk, breast, milk powder, comprise based on milk with based on the motion supplement of the motion supplement of non-milk, fruit juice such as the food additive of albumen spreading microgranule (protein sprinkle), comprises a day additional tablet, ablactational food and Yoghurt interior nutritional supplementation goods and powder or liquid form such as infant formula (formula), the milk replacer of larger infant formula (follow-on formula) or growth milk replacer.Similarly form provides useful suitable Halth-care composition herein.

In one embodiment, described compositions can also comprise antiviral agent, and perhaps reagent can make up with antiviral agent, for example is selected from theaflavin, protease inhibitor, Yolk immunoglobulin, synthetic sulphation sialic acid lipid NMSO ₃, human milk adhesion protein (glycoprotein of butterfat ball film), MUC1 mucin, cattle macromole lactalbumin part or above-mentioned combination one or more antiviral agent.In one embodiment, useful compositions comprises newborn component herein, perhaps with said composition and the simultaneously or sequentially administration of newborn component, this breast component is lactalbumin, lactalbumin part (comprising acidity or alkaline lactalbumin part or its combination), PROVON 190, lactoferrin, ferrum-lactoferrin, functional lactoferrin or ferrum-Lactoferrtin variants, functional lactoferrin or ferrum-lactoferrin fragment, vitamin D or calcium or above-mentioned any two or more combination in any for example.Preferably, said composition can also comprise lactoferrin, ferrum-lactoferrin, functional lactoferrin or ferrum-Lactoferrtin variants, functional lactoferrin or ferrum-lactoferrin fragment or above-mentioned any two or more combination, perhaps reagent can with above combination.

To digital scope disclosed herein (for example, quoting 1 to 10) to the whole rational numbers in this scope (for example also is intended to comprise, 1,1.1,2,3,3.9,4,5,6,6.5,7,8,9 and 10), and any range of the interior rational number of this scope (for example, quoting 2 to 8,1.5 to 5.5 and 3.1 to 4.7), therefore, whole subranges of the clear and definite disclosed four corner of this paper are disclosed herein clearly.Only enumerate the example with concrete intention, and think the whole possible combination that indicates clearly in a similar fashion in this application numerical value between cited minima and the maximum.

In this manual, when referenced patents description, other external file or out of Memory source, this is normally in order to provide contextual purpose for feature of the present invention is discussed.Except as otherwise noted, otherwise quoting of these external files is not understood to admit that these sources of these files or information are prior aries in any authority, perhaps forms the common practise part of this area.

The accompanying drawing summary

Two pictures of Fig. 1 represent, according to embodiment 2, with the G600 of (A) high CLA butterfat or the butterfat (B) bought from Fonterra Co-operative Group Limited ^TMThe percentage rate of infected cell not in the animal of ganglioside section processes.

Detailed Description Of The Invention

Examples prove hereinafter in the external cell attachment that prevents rotavirus, and has proved the ability of butterfat part treatment or prevention diarrhoea in the animal model that has infected the strain of Wa Human reoviruslike agent by various butterfat part.

1. definition

Term " anhydrous milkfat " and " AMF " use in this article interchangeably, and mean to come almost entirely except the butterfat part of anhydrating and non-fat material prepares by the phase reversal of rare butter or the dehydration of butter.AMF (, being also referred to as " anhydrous milk fat (anhydrousbutteroil) " if there is additive) prepares from rare butter of coming from full milk or butter usually, but also can be from the preparation of first Ruzhong.Bylund (Ed., 1995) discloses the common method of preparation AMF, and this list of references is intactly incorporated into herein.That preferred AMF is generally is about 60%, about 70%, about 80%, about 90%, about 95%, greater than about 95%, about 96%, about 97%, about 98%, about lipid of 99%, about 99.5% or 100%, and the AMF with lipid, particularly about 99% lipid, 99.5% lipid or higher lipid of about 98% to about 100% is preferred.For AMF or anhydrous milk fat, alimentary codex requires the moisture less than 0.2% usually, and for butter oil, alimentary codex requires the moisture less than 0.7% usually.Usually AMF further is separated into " firmly " (H) and " soft " (S) part, can also with " soft " (S) part further be separated into " soft or hard (soft hard) " (SH) and " soft (soft soft) " (SS) part, can be with soft (soft soft) " (SS) part further be separated into again " soft or hard (soft soft hard) " (SSH) with " soft soft (soft soft soft) " (SSS) part.The fatty acid composition that should be appreciated that every kind of part is different.The non-limiting example fatty acid composition of AMF and derivative moiety is shown in table 1 hereinafter to table 5.

The exemplary AMF of table 1. forms

Fatty acid component	Meansigma methods (%w/w)	Minima (%w/w)	Maximum (%w/w)
				C4:0 (butanoic acid)	3.6	3.3	4.1
C6:0 (caproic acid)	2.2	1.9	2.4
				C8:0 (sad)	1.2	1.1	1.4
C10:0 (capric acid)	2.6	2.2	2.8

C10:1 (2-decylenic acid)	0.3	0.3	0.3
				C12:0 (lauric acid)	2.9	2.5	3.2
C12:1 (11-dodecenoic acid)	0.1	0.1	0.1
				C13:0br (tridecanoic acid br)	0.1	0.1	0.1
C13:0 (tridecanoic acid)	0.1	0.1	0.1
				C14:0br (myristic acid br)	0.2	0.1	0.2
C14:0 (myristic acid)	10.4	9.5	10.8
				C14:1 (myristoleic acid)	0.9	0.6	1.0
c15:0iso br	0.4	0.3	0.5
				c15:0ante-iso br	0.6	0.5	0.7
C15:0 (pentadecanoic acid)	1.4	1.1	1.5
				c16:0br	0.3	0.2	0.3
C16:0 (Palmic acid)	28.7	25.4	30.4
				C16:1 (palmitoleic acid)	1.9	1.6	2.0
c17:0iso br	0.7	0.6	0.7
				c17:0ante-iso br	0.5	0.5	0.5
C17:0 (heptadecanoic acid)	0.7	0.6	0.8
				c17:1	0.3	0.3	0.4
C18:0 (stearic acid)	11.5	10.8	13.6
				C18:1 (oleic acid)	23.4	21.8	26.4
C18:2 (linoleic acid)	1.4	1.3	1.7
				c18:2conj	1.3	1.0	1.8
c18:3	0.8	0.7	0.9
				C20:0 (arachidic acid)	0.2	0.1	0.2
c20:1	0.3	0.2	0.3

The exemplary hard portion of table 2. (part H) forms

Fatty acid component	Meansigma methods (%w/w)	Minima (%w/w)	Maximum (%w/w)
				C4:0 (butanoic acid)	2.0	1.8	2.1
C6:0 (caproic acid)	1.3	1.2	1.4
				C8:0 (sad)	0.8	0.8	0.9
C10:0 (capric acid)	2.2	1.9	2.4
				C10:1 (2-decylenic acid)	0.2	0.1	0.2
C12:0 (lauric acid)	3.0	2.6	3.4
				C12:1 (11-dodecenoic acid)	0.0	0.0	0.1
C13:0br (tridecanoic acid br)	0.1	0.1	0.1
				C13:0 (tridecanoic acid)	0.1	0.1	0.1
C14:0br (myristic acid br)	0.1	0.1	0.2
				C14:0 (myristic acid)	11.8	10.7	12.6

C14:1 (myristoleic acid)	0.6	0.3	0.7
				c15:0iso br	0.4	0.3	0.5
c15:0ante-iso br	0.5	0.4	0.6
				C15:0 (pentadecanoic acid)	1.6	1.2	1.7
c16:0br	0.3	0.3	0.3
				C16:0 (Palmic acid)	34.8	31.5	36.6
C16:1 (palmitoleic acid)	1.3	1.1	1.6
				c17:0iso br	0.8	0.7	0.8
c17:0ante-iso br	0.5	0.5	0.6
				C17:0 (heptadecanoic acid)	0.9	0.8	0.9
c17:1	0.2	0.2	0.3
				C18:0 (stearic acid)	15.2	13.9	19.7
C18:1 (oleic acid)	17.0	15.5	19.8
				C18:2 (linoleic acid)	1.3	1.1	1.5
c18:2conj	0.8	0.6	1.1
				c18:3	0.5	0.4	0.6
C20:0 (arachidic acid)	0.2	0.2	0.3
				c20:1	0.2	0.1	0.2

The exemplary soft or hard part of table 3. (part SH) forms

Fatty acid component	Meansigma methods (%w/w)	Minima (%w/w)	Maximum (%w/w)
				C4:0 (butanoic acid)	4.0	3.7	4.3
C6:0 (caproic acid)	2.4	2.1	2.6
				C8:0 (sad)	1.2	1.1	1.4
C10:0 (capric acid)	2.4	2.2	2.7
				C10:1 (2-decylenic acid)	0.3	0.2	0.3
C12:0 (lauric acid)	2.5	2.3	2.7
				C12:1 (11-dodecenoic acid)	0.1	0.0	0.1
C13:0br (tridecanoic acid br)	0.1	0.1	0.1
				C13:0 (tridecanoic acid)	0.1	0.1	0.1
C14:0br (myristic acid br)	0.1	0.1	0.2
				C14:0 (myristic acid)	9.8	9.0	10.3
C14:1 (myristoleic acid)	0.8	0.5	0.9
				c15:0iso br	0.4	0.3	0.4
c15:0ante-iso br	0.5	0.4	0.6
				C15:0 (pentadecanoic acid)	1.4	1.1	1.5
c16:0br	0.2	0.2	0.3
				C16:0 (Palmic acid)	32.8	29.8	34.0
C16:1 (palmitoleic acid)	1.5	1.3	1.8
				c17:0isobr	0.6	0.6	0.7

c17:0ante-iso br	0.4	0.4	0.5
				C17:0 (heptadecanoic acid)	0.8	0.8	0.9
c17:1	0.3	0.2	0.3
				C18:0 (stearic acid)	13.2	12.5	16.1
C18:1 (oleic acid)	19.5	17.4	22.2
				C18:2 (linoleic acid)	1.3	1.2	1.5
c18:2conj	1.2	1.0	1.6
				c18:3	0.7	0.6	0.7
C20:0 (arachidic acid)	0.2	0.2	0.3
				c20:1	0.2	0.2	0.3

The exemplary soft or hard part of table 4. (part SSH) forms

Fatty acid component	Meansigma methods (%w/w)	Minima (%w/w)	Maximum (%w/w)
				C4:0 (butanoic acid)	4.0	3.9	4.3
C6:0 (caproic acid)	2.4	2.2	2.6
				C8:0 (sad)	1.4	1.2	1.6
C10:0 (capric acid)	2.8	2.4	3.4
				C10:1 (2-decylenic acid)	0.3	0.3	0.3
C12:0 (lauric acid)	3.2	2.7	3.8
				C12:1 (11-dodecenoic acid)	0.1	0.1	0.1
C13:0br (tridecanoic acid br)	0.1	0.1	0.1
				C13:0 (tridecanoic acid)	0.1	0.1	0.1
C14:0br (myristic acid br)	0.2	0.1	0.2
				C14:0 (myristic acid)	11.5	10.6	12.2
C14:1 (myristoleic acid)	0.9	0.7	1.0
				c15:0iso br	0.4	0.4	0.5
c15:0ante-iso br	0.6	0.6	0.7
				C15:0 (pentadecanoic acid)	1.4	1.2	1.5
c16:0br	0.3	0.2	0.3
				C16:0 (Palmic acid)	28.6	25.7	30.0
C16:1 (palmitoleic acid)	1.8	1.6	2.0
				c17:0isobr	0.7	0.6	0.7
c17:0ante-iso br	0.5	0.5	0.5
				C17:0 (heptadecanoic acid)	0.7	0.6	0.8
c17:1	0.3	0.3	0.4
				C18:0 (stearic acid)	10.6	10.2	11.3
C18:1 (oleic acid)	22.2	20.3	24.8
				C18:2 (linoleic acid)	1.4	1.3	1.5
c18:2conj	1.3	1.1	1.7
				c18:3	0.8	0.8	1.0

C20:0 (arachidic acid)	0.2	0.1	0.2
				c20:1	0.2	0.0	0.3

The exemplary soft soft part of table 5. (part SSS) forms

Fatty acid component	Meansigma methods (%w/w)	Minima (%w/w)	Maximum (%w/w)
				C4:0 (butanoic acid)	4.4	4.0	4.7
C6:0 (caproic acid)	2.7	2.4	2.8
				C8:0 (sad)	1.6	1.4	1.8
C10:0 (capric acid)	3.4	2.8	3.7
				C10:1 (2-decylenic acid)	0.4	0.3	0.4
C12:0 (lauric acid)	3.7	3.2	4.1
				C12:1 (11-dodecenoic acid)	0.1	0.1	0.1
C13:0br (tridecanoic acid br)	0.2	0.1	0.2
				C13:0 (tridecanoic acid)	0.1	0.1	0.1
C14:0br (myristic acid br)	0.2	0.2	0.2
				C14:0 (myristic acid)	10.2	9.5	11.0
C14:1 (myristoleic acid)	1.2	0.8	1.3
				c15:0iso br	0.5	0.4	0.5
c15:0ante-iso br	0.8	0.7	0.9
				C15:0 (pentadecanoic acid)	1.1	0.9	1.2
c16:0br	0.3	0.2	0.3
				C16:0 (Palmic acid)	20.0	18.4	21.1
C16:1 (palmitoleic acid)	2.6	2.2	3.0
				c17:0iso br	0.6	0.5	0.6
c17:0ante-iso br	0.5	0.5	0.5
				C17:0 (heptadecanoic acid)	0.4	0.4	0.5
c17:1	0.5	0.5	0.6
				C18:0 (stearic acid)	6.7	5.8	7.8
C18:1 (oleic acid)	30.8	28.2	33.4
				C18.2 (linoleic acid)	1.9	1.7	2.1
c18:2conj	1.7	1.3	2.3
				c18:3	1.3	1.1	1.4
C20:0 (arachidic acid)	0.1	0.1	0.1
				c20:1	0.3	0.1	0.4

Term " β-serum " expression from contain more than the milk flow point of 60% fat from the aqueous dairy component, as mentioned below, this separation is to realize by the phase reversal from O/w emulsion to water-in-oil emulsion.Rare butter is the preferred raw material for the preparation of β-serum.For example, as shown in Figure 2 among the WO2006/041316, the process for preparing butter oil (being also referred to as anhydrous milkfat or AMF) from rare butter, prepare β-serum.Preferably, the β serum is dry; Preferably, dry β-serum is powder.

Term " butterfat of high CLA " " is rich in the butterfat of CLA " with term and uses interchangeably, and expression butterfat, this butterfat comprises higher levels of suitable-9, anti--11CLA or its salt, ester or precursor than common butterfat, and randomly comprises higher levels of one or more other CLA isomers.The butterfat that is rich in CLA can prepare by known technology, and this technology includes but not limited to that the additional of free fatty of pasture breeding milk cow feed, and for example, comes feeding cow according to known method with fish oil and sunflower oil.Usually be rich in the butterfat of CLA from the full milk preparation, but also can prepare from colostrum.Described the common compositions of the butterfat that is rich in CLA among the disclosed international pct application WO2005/107736, this application is merged in herein by reference.The butterfat that is rich in CLA also can be by as mentioned below preparing with the additional butterfat of CLA.In one embodiment, the butterfat that is rich in CLA comprises the CLA at least about 2%, 4%, 6%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50% weight ratio, preferably suitable-9, anti--11CLA, or its salt, ester or precursor, and available scope (for example about 4% to about 7%) can selected between these aforementioned value arbitrarily.The butterfat that is rich in CLA preferably comprises suitable-9, anti--11CLA at least about 2% weight ratio, preferred about 2% to 10% weight ratio suitable-9, anti--11CLA, more preferably from about 4% to 7% weight ratio is suitable-9, anti--11CLA, and 5% weight ratio suitable-9, anti--11CLA most preferably from about.In one embodiment, the butterfat that is rich in CLA comprises the CLA isomer, this isomer comprises the CLA at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% weight ratio, preferred suitable-9, anti--11CLA or its salt, ester or precursor, and can select arbitrarily available scope (for example about 80% to about 95%) between these aforementioned value.The butterfat that is rich in CLA preferably comprises the CLA isomer, and this isomer comprises suitable-9, anti--11CLA at least about 50% weight ratio, preferred about 70% to 80% weight ratio suitable-9, anti--11CLA.

In this description used term " comprise " expression " at least in part by ... form ".When in explaining present disclosure, comprising the narration of this term, in each narration or claim, all must exist with the initial feature of this term, but further feature also can exist.Relational language such as " comprising (comprise) " and " comprising (comprised) " is explained in the same manner.

Term " conjugated linoleic acid " (CLA) represents one or more CLA isomers, this isomer is selected from 9 of free or esterified form, 11-octadecadienoic acid and 10,12-octadecadienoic acid, or its salt, or its mixture, this isomer comprises suitable-9, suitable-11, suitable-9, instead-11, instead-9, suitable-11, instead-9, instead-11, suitable-10, suitable-12, suitable-10, instead-12, trans-10, suitable-12 and trans-10, anti-12 isomers, preferably suitable-9, suitable-11, suitable-9, instead-11, trans-10, suitable-12 and suitable-10, suitable-12 isomers, as in disclosed US Patent No. 5, described in 585,400, this patent is merged in herein by reference.Chin et al (1992) has described such as CLA natural origin suitable-9, anti--11CLA, and this natural origin comprises animal, antibacterial and plant origin.Can linoleic acid be changed into CLA by the fermentation of following antibacterial: for example, produce brood cell clostridium (Clostridiumsporogenes), Clostridium bifermentans (Clostridium bifermentans), mud clostridium (Clostridium sordellii) and bacteroid (Bacteroides sp) (Verhulst, et al., 1985).Other organism that is used for bacterial fermentation comprises Butyrivibrio fibrisolvens (Butyrivibriofibrisolvens), eubacterium lentum (Eubacterium lentum), propionibacterium freudenreichii (Propionibacterium freudenreichi), bacillus acidophilus (Lactobacillusacidophilus), Lactobacillus reuteri (Lactobacillus reuteri), Erichsen megacoccus (Megasphaera elsdenii) and bifidobacterium breve (Bifidobacterium breve).Contain respectively the preparation that 65% and 76% the linoleic sunflower oil Flos Carthami oil of having an appointment can be used for CLA.

" effective dose " is to give therapeutic effect needed amount.The people such as Freireich (1966) have described animal and human's dosage mutual relation (based on milligram/square metre surface).Can approximately determine body surface area from height and the body weight of individuality.Referring to, Scientific Tables (science tabulation) for example, Geigy Pharmaceuticals, Ardley, New York, 1970,537.As understood by those skilled in the art, effectively dosage also changes along with the use of route of administration, carrier etc.

Term " is rich in (enrich) " and the concentration height of the appointment composition that the concentration ratio of the appointment composition that " being rich in (enriched) " expression part or compositions have exists in female part (parent fraction) in full milk, rare butter, butter, anhydrous milkfat, buttermilk, butter serum or β serum or described part or compositions source.The part that for example is rich in ganglioside is the part with ganglioside lipid concentration higher than full milk, rare butter, butter, anhydrous milkfat, buttermilk, butter serum or β serum.Similarly, the part that is rich in phospholipid is the part with phospholipid concentration higher than full milk, rare butter, butter, anhydrous milkfat, buttermilk, butter serum or β serum.

The compositions that term " part " expression is separated from source material, and said composition forms different from the source material of isolating described part.For example, non-human mammal butterfat part, for example sheep, goat, pig, Mus, Babalus bubalis L., camel, yak, horse, donkey, yamma or butter fat part, preferred butter fat part is different from the composition of naturally occurring butterfat in the full milk.In selectable embodiment, the concentration in the described part is higher than full milk, or full colostrum, or from rare butter of breast, or from rare butter of colostrum, or from the AMF of breast, or from the concentration among the AMF of colostrum.Useful preferred source material comprises full milk, rare butter, anhydrous milkfat, buttermilk, butter serum or β serum or from the rare butter of the milk surum of Lac Bovis seu Bubali herein.As described herein, preferred part is lipid part.

Therefore, the separating part of term " is rich in the butterfat part of phospholipid " expression non-human mammal butterfat, wherein the phospholipid concentration of this part is higher than the phospholipid concentration of naturally occurring non-human mammal butterfat.Preferably, at least a phospholipid in the useful part herein, or the naturally occurring non-human mammal butterfat of the concentration ratio of at least a phospholipid and at least a ganglioside in the concentration height at least about 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%, and can between these values, select available scope.In selectable embodiment, the concentration in the described part is higher than full milk, or full colostrum, or from rare butter of breast, or from rare butter of colostrum, or from the AMF of breast, or from the concentration among the AMF of colostrum.

Similarly, the separating part of term " is rich in the butterfat part of ganglioside " expression non-human mammal butterfat, wherein the ganglioside lipid concentration of this part is higher than the phospholipid concentration of naturally occurring non-human mammal butterfat.Preferably, at least a ganglioside in the useful part herein, or the concentration height in the naturally occurring non-human mammal butterfat of the concentration ratio of at least a ganglioside and at least a phospholipid is at least about 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95 or 100%, and can select effective scope between these values.In selectable embodiment, the concentration in the described part is higher than full milk, or full colostrum, or from rare butter of breast, or from rare butter of colostrum, or from the AMF of breast, or from the concentration among the AMF of colostrum.

Term " functional lactoferrin fragment " is intended to represent the natural existence of lactoferrin polypeptide or the part that non-natural exists, and when measuring according to hereinafter embodiment, this part has activity and comprises the metal ion functional fragment.The metal ion binding fragment that useful lactoferrin fragment comprises that the metal ion of lactoferrin polypeptide, the lactoferrin of truncate produces in conjunction with hydrolysate, the fragment that comprises N-lobule (lobe) metal ion binding pocket (binding pocket), the fragment that comprises C-lobule metal ion binding pocket and (by artificial or natural process) and identifies by the known technology of hereinafter discussing.Disclosed International Patent Application WO 2006/054908 and WO 2007/043900 have reported preparation and the purposes of lactoferrin fragment, and each application is merged in herein by reference.

The variant of the activated lactoferrin polypeptide of tool when term " functional Lactoferrtin variants " is intended to represent measure according to example hereinafter, and comprise the functional variant of metal ion.

Term " lactoferrin polypeptide " means non-glycosylated or glycosylated wild type lactoferrin aminoacid sequence or from the homology lactoferrin sequence of all those species as described below.Therefore lactoferrin polypeptide has two metal ion binding pockets, can be according to the stoichiometry of 2 metal ions of each lactoferrin molecule bind metal ion recently.A metal ion binding pocket is positioned at the N end lobule (N-lobule) of lactoferrin, and another bag is positioned at C end lobule (C-lobule).The sequence of the checking of cattle and people's lactotransferrin (lactoferrin precursor), lactoferrin and peptide wherein can be referring to Swiss-Prot (http://au.expasy.org/cgi-bin/sprot-search-ful).The lactoferrin polypeptide that indicates comprises Lac Bovis seu Bubali transferrin precursor accession number P24627, Bovine Lactoferrin, people's lactotransferrin precursor accession number P02788 and human lactoferrin.Disclosed International Patent Application WO 2006/054908 and WO 2007/043900 have reported preparation (comprising separating from the Ruzhong) and the purposes of lactoferrin polypeptide, its fragment, hydrolysate and aminoacid sequence, and each application is merged in herein by reference.Lactoferrin polypeptide can be in conjunction with the metal ion of " natural " level, normally iron ion.For example, Bovine Lactoferrin is that natural about 10% to 20% (preferred 15%) ferrum is saturated.This paper can use the saturated Apolactoferrin of at least 1% metal ion (apolactoferrin) and lactoferrin.

Term " metal ion lactoferrin ", " lactoferrin that metal ion is saturated ", " metal ion lactoferrin fragment " and " the lactoferrin fragment that metal ion is saturated " are intended to represent to provide the lactoferrin polypeptide of colony of metal ion binding pocket or the colony of fragment, and what wherein exist in this colony has the metal ion of combination at least about 25% metal ion binding pocket.Should be appreciated that described colony can comprise the polypeptide of different plant species; For example, some molecules are coupled ion not, and other molecule each in conjunction with 1 or 2 ion.In the situation of using the different metal ion, some molecules can bind metal ion, this metal ion for example is selected from other ion of aluminum, bismuth, copper, chromium, cobalt, gold, ferrum, manganese, osmium, platinum, ruthenium, zinc ion or specificity cooperation in lactoferrin metal ion binding pocket, and other molecule can be in conjunction with different ions.In some cases, described colony can comprise the polypeptide relevant with non-specific ions binding, wherein one or more ions, and the preferable alloy ion is non-specific binding, that is, be not combined with polypeptide in the metal ion binding pocket.Can be calcium and selenium with the limiting examples of the ion of lactoferrin polypeptide non-specific binding.Can realize the variation of saturation, and can adopt spectrophotometric analysis to determine that this saturation-for example referring to disclosed International Application No. WO 2007/043900, this application is merged in herein by reference by known method.In one embodiment, exist in the colony of lactoferrin molecule at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or 100% metal ion binding pocket has the metal ion of combination, and available scope (for example, about 5% to about 100% can selected between the aforementioned value arbitrarily, about 10% to about 100%, about 15% to about 100%, about 20% to about 100%, about 25% to about 100%, about 30% to about 100%, about 35% to about 100%, about 40% to about 100%, about 45% to about 100%, about 50% to about 100%, about 55% to about 100%, about 60% to about 100%, about 65% to about 100%, about 70% to about 100%, about 75% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to about 100% and about 99% to about 100%).

Term " butterfat " comprises mammal lipid and lipid part, lipid hydrolysis thing and lipid part hydrolysate.In certain embodiments, butterfat can be any mammal butterfat, includes but not limited to cattle, sheep, goat, pig, Mus, Babalus bubalis L., camel, yak, horse, donkey, yamma or people's butterfat, and wherein butter fat is preferred source.Preferred milk fat is fat of dairy product, particularly butter fat.Preferred milk fat contains one or more Palmic acid, oleic acid, stearic acid or myristic acid, and they are as the abundantest fatty acid that exists, and preferably, Palmic acid, oleic acid, stearic acid and myristic acid are the abundantest fatty acids that exists.In particularly preferred embodiments, butterfat such as rare butter or AMF, (about 23% (w/w) is to about 32% (w/w) for example to have a) Palmic acid with the substantially the same percentage by weight of common butter fat, common about 28% (w/w)-referring to table 1.2, PF Foxand PLH McSweeney eds, Advanced Dairy Chemistry Volume 2-Lipids, 3rdEd, Springer NY, NY (2006) ISBN-10:0-387-26364-0); B) with the oleic acid of the substantially the same percentage by weight of common butter fat (about 15% (w/w) be to about 22% (w/w), and common about 17% (w/w)-referring to Fox and McSweeny is with above); C) with the stearic acid of the substantially the same percentage by weight of common butter fat (about 10% (w/w) be to about 15% (w/w), and about 12% (w/w)-referring to Foxand McSweeny is with above usually); D) with the myristic acid of the substantially the same percentage by weight of common butter fat (about 9% (w/w) be to about 12% (w/w), and about 11% (w/w)-referring to Fox andMcSweeny is with above usually); E) above-mentioned a), b), c) or d) in any two kinds; F) above-mentioned a), b), c) or d) in any three kinds; G) above-mentioned a), b), c) and d) in each.Anhydrous milkfat (AMF) is preferred, particularly has the AMF that forms with Palmic acid, oleic acid and the stearic acid of the substantially the same percentage by weight of common butter fat, more preferably has the AMF (referring to Fox and McSweeny, together above) that the fatty acid substantially the same with common butter fat forms.Preferred butterfat part also comprises rare butter, butter, anhydrous milkfat (AMF) (Dehydration of the phase reversal by rare butter or butter is standby usually), buttermilk, the butter serum, the β serum, come the hard butterfat part in one or more stages of self-separation (to comprise H, SH and SSH part), come the soft butterfat part in one or more stages of self-separation (to comprise S, SS and SSS part), the combination of hard butterfat part, the combination of soft butterfat part, the combination of hard butterfat part and soft butterfat part, the sphingolipid part (comprises the sphingomyelins part, the ceramide part, cerebroside part or ganglioside part or above-mentioned any two or more combination in any), butterfat ball membrane lipid part, phospholipid moiety and complex lipid part or above-mentioned any two or more combination in any and above-mentioned any one or multiple hydrolysate and part of hydrolysate, the arbitrarily combination of two or more hydrolysates and the combination of one or more hydrolyzable moieties and/or one or more non-hydrolyzable moieties.Preferably, described butterfat comprises at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99% or 100% lipid, and can (for example select available scope between these values arbitrarily, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 85% to about 100%, about 90% to about 100%, about 95% to about 100%, about 96% to about 100%, about 97% to about 100%, about 98% to about 100% and about 99% to about 100%, preferred about 40% or be higher than 40% to about 100%).

That term " oral administration " comprises is oral, mouthful cheek, enteral and gastric administration.

Term " parenteral " includes but not limited to part (comprising any skin, epidermis or skin and mucocutaneous administration), subcutaneous, intravenous, intraperitoneal, intramuscular administration.

Term " medicine acceptable carrier " is intended to represent to include but not limited to the carrier of excipient, diluent, auxiliary agent or its combination, when the dosage of the chemical compound that will be enough to send useful effective dose herein or compositions carried out administration, described carrier can carry out administration to individuality and not reduce the active of said composition and do not have toxicity as the component of compositions as herein described.Preparation can oral administration, intranasal administration or parenteral (comprising topical, intramuscular administration, intraperitoneal administration, subcutaneous administration and intravenous administration).

" individuality " is animal, preferred mammal, more preferably mammal companion animal (companionanimal) or people.Preferred companion animal comprises cat, Canis familiaris L. and horse.In one embodiment, adult, child or the baby of artificial adult, child or baby or immunocompromised host.

Term " treatment " or its derivative should be interpreted as its most extensive possible connotation.This term should not be understood to hint individuality is treated until return to one's perfect health.Therefore, " treatment " broadly comprise improvement and/or the prevention to the seriousness of paresthesia epilepsy or concrete state.

2. butterfat separates with butterfat

Fox and McSweeney (2006) has discussed butterfat comprehensively, and this list of references is merged in herein by reference.Except lipid, butterfat also comprises vitamin, sterol and less component.Referring to the chapter 1 Composition and Structure of BovineMilk Lipids (compositions of Lac Bovis seu Bubali lipid and structure) of Fox and McSweeney, be used for describing naturally occurring butter fat.Dairy Processing Handbook (Dairy Processing handbook), 1995 and Illingworth, 2002, and the people such as Rombaut, 2006 (b) have discussed the separation of butterfat, and these lists of references all are merged in herein by reference.Fox and McSweeney (2006) has discussed the seasonal variations of butterfat.

The example of useful butterfat part comprises rare butter (usually about 20% fat to about 40% weight ratio, the fat of preferred about 40% weight ratio), butter, butter, anhydrous milkfat (AMF) (Dehydration of the phase reversal by rare butter or butter is standby usually), buttermilk, butter serum, β serum, hard butterfat part, soft butterfat part, sphingolipid part, butterfat ball membrane portions, phospholipid moiety and complex lipid (lipid of each 3 kinds of molecule generation or more eurypalynous hydrolysate) partly and above-mentioned combination and above-mentioned hydrolysate among the present invention.

Bylund for example, 1995, Rombaut et al, 2005; Rombaut et al, 2006 (a); Rombaut et al, 2006 (b) and disclosed International Application No. WO 2006/041316 have been discussed buttermilk, butter serum and β serum, and all these lists of references are merged in herein by reference.Buttermilk is to describe the term that adopts cream preparation method aqueous solution bulk phase of acquisition from conventional cream is produced, and this cream preparation method can be batch (churning (churn)) method or continuous (Fritz) method.Buttermilk also is the term of describing the aqueous by-product that is produced by the rare butter concentration step the conventional method for preparing AMF from rare butter.This conventional method relates to the concentrated preparation oil that then transfers on the contrary of rare butter, and is should oil further concentrated and grind (polish) and prepare AMF.At last, buttermilk also is to describe the secondary degreasing thing (secondary skim) of two serums (two-serum) method that AMF produces and the term of the combination of β serum by-product, for example referring to Bylund (Ed., 1995) and disclosed International Application No. WO 2006/041316 (referring to Fig. 2), these lists of references have described this method in detail.In this two serums method, will further be separated by the by-product that rare butter concentration step obtains and produce the secondary degreasing thing, and will prepare β-serum further the separation from the by-product that oily concentration step obtains.In the first two example, preparation buttermilk before any phase reversal occurs.In the 3rd example, buttermilk is the combination of the β serum for preparing after the secondary degreasing thing of preparation before the phase reversal and the phase reversal.In these methods, usually realize concentrated and grinding by centrifugal.Usually realize phase reversal by homogenization.The source that should be appreciated that these milk lipid parts can be breast or colostrum or its combination.

Useful raw material comprises rare butter, AMF, buttermilk, butter serum or the β serum that obtains from breast or colostrum or its combination in the separation.

Can carry out by the difference crystallization multiple stage separation (multistage fractionation) of butterfat.Butterfat partly is heated to the temperature of setting, and the part of fractional crystallization or solid (" tristearin "-hard portion) part and liquid (" olein "-soft part) part.Multiple stage separation means the again separation in the subsequent step of the product of separating step formerly.Can prepare continuous soft part by the soft part of mother being separated into soft hard thin part (sub-fraction).

Other partition method comprises that phase reversal, ester exchange, glycerolysis, separated from solvent (for example adopting separately or sequentially ethanol, water or acetone), supercritical separate (for example referring to Astaire, et al, 2003), the separation of nearly critical separation (for example referring to WO 2004/066744), distillation, centrifugalize, suspension crystallization, drying crystalline, use modifier (for example soap or emulsifying agent), ultrafiltration, microfiltration and any method of separating for lipid known in the art and the combination of these methods, all these methods all are known in the art.

In one embodiment, the separated from solvent that separation method is selected from separately or order utilizes ethanol, water or acetone that rare butter, AMF, buttermilk, butter serum or β serum are carried out.

The lipid that exists in the present composition can be by completely or partially modification, no matter be natural, chemical, enzymatic, or by arbitrarily other method known in the art, these lipids comprise, the lipid of for example, glycosylation, sialylated, esterification, phosphorylation or hydrolysis.The lipid hydrolysis thing can utilize known technology to prepare, this known technology includes but not limited to acid hydrolysis, basic hydrolysis, such as the enzyme hydrolysis that utilizes lipase and the microbial fermentation of Fox and the described enzyme hydrolysis of McSweeney ((2006), Chapter 15by HC Deeth and CH Fitz-Gerald).A kind of method of basic hydrolysis comprises adds 1%KOH (being dissolved in ethanol), and heats 10 minutes.The material of hydrolysis can neutralize with acetic acid or hydrochloric acid.

Butterfat ball membrane material can be according to Kanno ﹠amp; Dong-Hyun, 1990 acidization tool separates, and can pass through such as Kanno et al, and the method for 1975 described interpolation methanol further is separated into lipid and protein portion with butterfat ball membrane material.According to Purthi et al, 1970 step can be come the separating phospholipids part by utilizing the acetone extract lipid mixture.By the selective extraction of pentane to non-polar lipid, the lipid residue can further be enriched in the butterfat ball membrane lipid.

Disclosed International Patent Application WO 2006/041316, WO 2007/123424 and WO2007/123425 have also described the separation method for the preparation of useful butterfat part herein, and each application is integrally incorporated into herein by reference.

Useful particularly preferred butterfat those butterfat parts of partly being included in the part of the butterfat of those described in the embodiment hereinafter and in following table, summing up herein.These parts can be emulsion or drying, also can be powder, and this part randomly adds to improve liquidity with the component that contains such as the fluidizer of lactose.

Table 6-butterfat part

＜0.01=trace

3. the useful compositions of inventing

Useful herein compositions can be formulated as food, beverage, food additive, beverage additive, supplementary, nutriment, medicated food, enteral or parenteral feed product, for meal, cosmeceutical or medicine (pharmaceutical).Those skilled in the art can prepare suitable preparation according to the instruction of technical ability and this description.

In one embodiment, useful compositions comprises any edible consumer goods that can be loaded with lipid herein.The example of suitable edible consumer goods comprises powder, liquid, comprise chocolate, gel, ice cream is at interior pan work, the fruit product of reduction, snacks bar (snackbars), food bars, the muesli bar, tablespread, sauce dips in liquid, comprises the milk product of Yoghurt and cheese, comprise based on milk with based on the beverage (for example milk beverage and boruga) of the beverage of non-milk, milk powder comprises based on milk with based on the motion supplement of the motion supplement of non-milk, such as the food additive of albumen spreading microgranule, comprise a day additional tablet, ablactational food and yoghourt interior nutritional supplementation goods and powder or liquid form exist such as infant formula, the milk replacer of larger infant formula or growth milk replacer.In this embodiment, useful preferred composition can be the infant formula of powder or liquid form, larger infant formula or growth milk replacer herein.Can provide suitable Halth-care composition useful among the present invention with similar form.

Powder or liquid form such as infant formula, the example of the milk replacer of larger infant formula or growth milk replacer comprises following example.Useful infant formula herein, an example of larger infant formula or growth milk replacer comprises (w/w)

(a) lactose of 30%-60%

(b) vegetable oil of 15%-35%

(c) skim milk of 0%-40%

(d) lactalbumin of 0%-40%, for example WPC or WPI, preferred 80% WPC (WPC80)

(e) the useful reagent herein of 1%-50%.

Useful infant formula herein, another example of larger infant formula or growth milk replacer comprises (w/w)

(a) lactose of 40%-60%

(b) vegetable oil of 20%-30%

(c) skim milk of 10%-15%

(d) lactalbumin of 6%-8%, preferred WPC80

(e) the useful reagent herein of 1%-10%.

(a) lactose of 40%-60%

(b) vegetable oil of 20%-30%

(c) skim milk of 10%-15%

(d) lactalbumin of 6%-8%, preferred WPC80

(e) the useful reagent herein of 1%-5%.

(a) lactose of 40%-60%

(b) vegetable oil of 20%-30%

(c) skim milk of 10%-15%

(d) lactalbumin of 6%-8%, preferred WPC80

(e) the useful reagent herein of 2%-5%.

Useful infant formula among the present invention, another example of larger infant formula or growth milk replacer comprises (w/w)

(a) lactose of 30%-60%

(b) vegetable oil of 15%-35%

(c) skim milk of 0%-40%

(d) lactalbumin of 0%-40%, preferred WPC80

(e) the useful reagent herein of 1%-50%, for example β serum powder or its part, perhaps β serum powder and its part are such as the part that obtains from the β serum that is rich in polar lipid or lacks in neutral lipid.

(a) lactose of 40%-60%

(b) vegetable oil of 20%-30%

(c) skim milk of 10%-15%

(d) lactalbumin of 6%-8%, preferred WPC80

(e) the useful reagent herein of 1%-5%, for example β serum powder or its part, perhaps β serum powder and its part are such as the part that obtains from the β serum that is rich in polar lipid or lacks in neutral lipid.

These any infant formulas can also comprise 0.1%w/w to 4%w/w, one or more vitamin premix (premix), mineral premix, phosphatidylcholine, one or more antioxidants, one or more stabilizing agents or one or more nucleotide of preferred 2%w/w to 4%w/w/ or above-mentioned any two or more combination.In certain embodiments, can prepare the heat that these infant formulas provide 2700kJ/L to 3000kJ/L.

In selectable embodiment, can prepare useful compositions herein and allow approach by any selection to individual administration, this approach includes but not limited to oral or parenteral (comprising topical, subcutaneous administration, intramuscular administration and intravenous administration).

Therefore, can prepare useful pharmaceutical composition of the present invention with suitable medicine acceptable carrier (comprising excipient, diluent, auxiliary agent and combination thereof), and select this carrier according to the expectation approach of administration and standard drug practice.For example, useful compositions of the present invention can be carried out oral administration with the form of powder, liquid, tablet or capsule, perhaps carries out topical with the form of ointment, emulsifiable paste or washing liquid.Suitable preparation can contain required additive (additionalagent), comprise emulsifying agent, antioxidant, flavoring agent or coloring agent, and can make this suitable preparation be applicable to rapid release, slow release (delayed release), modified release (modified release), slow release (sustained release), pulse release or controlled release.

Capsule can contain such as the acceptable material of the medicine of gel or cellulosic any standard.Can be according to conventional steps, by the mixture of active component and solid carrier and lubricant is suppressed to prepare tablet.The example of solid carrier comprises starch and sugared bentonite.Active component also can carry out administration to contain the binding agent such as lactose or mannitol, the filler of routine and the duricrust tablet of tablet agent or the form of capsule.Pharmaceutical composition also can carry out administration by parenteral route.The example of parenteral dosage forms comprises aqueous solution, isotonic saline solution or contains 5% glucose solution of activating agent, or the acceptable excipient of other known medicine.Cyclodextrin or other solubilizing agent well known by persons skilled in the art can come for delivering therapeutic agents as drug excipient.

The effectiveness of useful compositions of the present invention can be assessed in vitro and in vivo.For example referring to following instance.In brief, can test the ability that described compositions suppresses external rotavirus infection.For studying in the body, can feed or inject described compositions to animal (for example mice), then estimate said composition to the effect of viral infection.Based on result of study, can determine suitable dosage range and route of administration.

Useful compositions can be used individually or use with one or more other therapeutic combination ground herein.This therapeutic agent can be food, beverage, food additive, beverage additive, food component, beverage ingredient, supplementary, nutriment, medicated food, health product, medicine (medicament) or medicine (pharmaceutical).Described therapeutic agent preferably weakens the symptom of one or more rotavirus infections effectively.

When using with other therapeutic combination, administration useful compositions and other therapeutic agent herein simultaneously or sequentially.Simultaneously administration comprises administration or the basically administration of while of different dosage form of the single dosage form that comprises whole components.The order administration comprises administration according to different schemes, is preferably to provide useful compositions and the cycle of other therapeutic agent to exist overlapping herein.

Can with useful herein compositions altogether the suitable agent of administration (co-administered) comprise antiviral agent, theaflavin, protease inhibitor, Yolk immunoglobulin, synthetic sulphation sialic acid lipid NMSO ₃, human milk adhesion protein (glycoprotein of butterfat ball film), MUC1 mucin, cattle macromole lactalbumin part and above-mentioned combination, and other suitable reagent known in the art.

In one embodiment, herein useful compositions comprise newborn component or with the simultaneously or sequentially administration of newborn component, this breast component is lactalbumin, lactalbumin part (comprising acidity or alkaline lactalbumin part or its combination), PROVON 190, lactoferrin, ferrum-lactoferrin, functional Lactoferrtin variants, functional lactoferrin fragment, vitamin D or calcium or above-mentioned combination for example.The useful compositions that contains newborn component for example comprises, food, beverage, food additive, beverage additive, supplementary, nutriment, medicated food and health product.Also can adopt the newborn part that is rich in these components.Described useful lactoferrin, fragment and compositions in International Patent Application WO 03/082921 and WO 2007/043900, these two applications are incorporated into this paper by integral body herein by reference.

Should be appreciated that and also can adopt in the method for the invention above listed other therapeutic agent (based on reagent and the medicament of food), wherein this therapeutic agent respectively, simultaneously or sequentially with useful herein compositions administration.

Be to be understood that, depend on following variable situation, the dosage of the compositions of administration, administration cycle and conventional administering mode are different between the patient: such as the seriousness of individual symptom, the pattern of wanting sanatory type, selection administration, individual age, sex and/or general health.But, as general example, the inventor thinks the about 1mg of every kg body weight administration every day to the useful compositions herein of about 1000mg, and the preferred about 50mg of every kg every day is about 500mg extremely, perhaps 150mg/kg/ days to about 410mg/kg/ days, or about 110mg/kg/ days to about 310mg/kg/ days.In one embodiment, the inventor thinks the herein useful pharmaceutical composition of the about 0.05mg of every kg body weight administration to about 250mg.

Should be appreciated that administration can comprise the administration of the every daily dose of single, or the administration of suitable repeatedly discontinuous fractionated dose.

By reference following examples, will various aspects of the present invention be described in unrestriced mode.

Embodiment

Sample analysis

Protein level multiply by 6.38 by total nitrogen to be determined.The phospholipid level is passed through ³¹P NMR determines.The ganglioside lipid level is determined by the following method.The powder of three parts of about 0.1g is weighed in the kimax of 16ml test tube and record weight.Add the methanol of 6ml and by eddy current mixing 1min.Solution is hatched 10min under 50 ℃, then add 6ml water and mix by eddy current.Solution is left standstill 2hr come sedimentation under 4 ℃, sample is taken out and passes through the filter of 0.45 μ m.Analyze this sample by HPLC.Use is with NH2 protection (security guard) (Phenomenex ^TMPhenomenex in the KJO-4282 column sleeve (holder) ^TMAJO-4302) Cosmosil ^TM5NH2-MS waters post (Nacalai Tesque Inc, USA).All change guard column (guard cartrige) every day of analyzing.With sample feeding in post, and adopt solvent orange 2 A (90% acetonitrile, 5% water and 5% 5mM phosphate buffer pH5.6) and solvent B (50% acetonitrile, 45% water and 5% 200mM phosphate buffer pH5.6), carry out eluting with the flow velocity of 2ml/min.Adopt following gradient: 100% A keeps 3.5min, then in the 26.5min by the A of 100% A to 55%, then in the 1min by the A of 55% A to 100%, then 100% A keeps 5min (Wagener et al. (1996), Journal of Lipid Research 37,1823-1829).Adopt buttermilk GD3 (Matreya#1504) to generate the external standard curve of 0 μ g to 2 μ g GD3.Under 203nm, monitor eluting.

The preparation of lipid and other dairy material

Butterfat part (comprising the β serum), lactoferrin, Sialyl Oligolac ^TMBreast extract and butterfat ball film (MFGM) material are provided by Fonterra Co-operative Group Limited (New Zealand).Sialyl Oligolac ^TMThe breast extract is the spray-dried powders that is derived from colostrum, and this breast extract contains high-level genuine milk oligosaccharide, mineral and sialic acid free and that be combined with carbohydrate (protein ((former state (as is)) 8.7%, lactose 61.7%, moisture 3.9%, fat 0.08%, ash 18.9%, free sialic acid 2.5mg/g, the sialic acid 9.3mg/g of combination).Sialyl Oligolac ^TMContain 3 ' sialyl lactose and two sialyl lactoses, they are respectively the free form of the polysaccharide that is derived from Ganglioside GM3 and GD3.MFGM in the table 9 and MFGM protein part are prepared by New Zealand's butterfat according to known method.

AMF and AMF part

The AMF, AMF hard portion (SH and SSH) and the soft part of AMF (SSS) that are provided by Fonterra Co-operative Group Limited have been described hereinbefore.

The butterfat of high CLA contains 5.4% CLA, and then prepares anhydrous milkfat by the breast that produces according to known method with fish oil and sunflower oil feeding cow and prepare.Described the common compositions of the butterfat that is rich in CLA in disclosed international pct application WO 2005/107736, this application is merged in by reference at this.

Phospholipid moiety

More than described in table 7 and in following examples employed part 7 to 11 according to please WO 2006/041316 described method in the disclosed international monopoly preparing (referring to embodiment 3 to 6).Part 12 prepares by the supercritical carbon dioxide extraction of the phospholipid moiety 10 in the table 7.Part 15 prepares by the alcohol extraction of β serum powder.

Alcohol extraction by β serum powder prepares Phospholipid Concentrate PC500TM phospholipid moiety (from Fonterra Co-operative Group Limited, New Zealand).The β serum is the liquid phase that produces in the AMF preparation.The PC500TM phospholipid moiety is spray-dired newborn phospholipid concentrate, and it is common to consist of 77% to 95% TL, about 50% neutral lipid and about 30% polar lipid; And common iipidomic becomes 1.5% to 5% Phosphatidylserine, 12% to 18% phosphatidylcholine, 6% to 9% PHOSPHATIDYL ETHANOLAMINE and 6.7% to 9% sphingomyelins; And common fatty acid consists of butanoic acid (4:0) 1.8%, capric acid (10:0) 0.3%, lauric acid (12:0) 0.5%, myristic acid (14:0) 7.4%, myristoleic acid (14:1) 14.1%, pentadecanoic acid (15:0) 1.0%, Palmic acid (16:0) 26.0%, palmitoleic acid (16:1) 1.7%, heptadecanoic acid (17:0) 0.6%, heptadecenoic acid (17:1) 0.3%, stearic acid (18:0) 11.9%, oleic acid (18:1) 39.0%, linoleic acid (18:2) 5.0%, linolenic acid (18:3) 2.0%, arachidic acid (20:0) 0.3% and cholesterol 0.8%.

Pass through PC500 ^TMThe acetone extract of phospholipid moiety prepares Phospholipid ConcentratePC600 ^TMPhospholipid moiety (from Fonterra Co-operative Group Limited, New Zealand).PC600 ^TMPhospholipid moiety is cryodesiccated newborn phospholipid concentrate, and it is common to consist of 75% polar lipid, 8.0% neutral lipid, the ash less than 12% and less than 4% moisture; Common iipidomic becomes 3% to 4% Phosphatidylserine, the phosphatidylcholine greater than 36%, the PHOSPHATIDYL ETHANOLAMINE greater than 9% and greater than 18% sphingomyelins; And common fatty acid consists of myristic acid (14:0) 6.6%, Palmic acid (16:0) 27.1%, palmitoleic acid (16:1) 1.3%, heptadecanoic acid (17:0) 2.3%, stearic acid (18:0) 14%, oleic acid (18:1) 38.2%, linoleic acid (18:2) 6.5%, linolenic acid (18:3) 2%, cholesterol 0.1% and other 2%.

Pass through PC500 ^TMThe aqueous extraction of phospholipid moiety (coming unstuck) prepares PhospholipidConcentrate PC700 ^TMPhospholipid moiety (from Fonterra Co-operative Group Limited, New Zealand).PC700 ^TMPhospholipid moiety is lyophilization breast phospholipid concentrate, and it is common to consist of 85% lipid, 10% ash, 2% lactose and 2.5% moisture; Common iipidomic becomes Phosphatidylserine 3%, phosphatidylcholine 31%, PHOSPHATIDYL ETHANOLAMINE 8.7% and sphingomyelins 16.5%; And common fatty acid consists of myristic acid (14:0) 5.4%, Palmic acid (16:0) 20.9%, palmitoleic acid (16:1) 1.3%, heptadecanoic acid (17:0) 0.5%, stearic acid (18:0) 10.5%, oleic acid (18:1) 30.5%, linoleic acid (18:2) 4.3%, linolenic acid (18:3) 1.8% and arachidonic acid 0.5%.

The ganglioside part

More than described in table 7 and in following examples employed part 7 to 11 prepare (referring to embodiment 3 to 6) according to disclosed International Patent Application WO 2006/041316 described method.Part 12 prepares by the supercritical carbon dioxide extraction of phospholipid moiety in the table 7 10.Part 15 prepares by the alcohol extraction of β serum powder.

Alcohol extraction by β serum powder prepares G500 ^TMAnd G600 ^TMGanglioside part (from Fonterra Co-operative Group Limited, New Zealand).The β serum is the liquid phase that produces in the AMF preparation process.

G500 ^TMGanglioside partly is spray-dired newborn ganglioside concentrate, has wherein added lactose and WPC (Lactalbumin concentrate) to improve powder flowbility.G500 ^TMCommon lipid 34.0%, moisture 3.2%, ash 5.0% and the lactose 56.0% of consisting of of ganglioside part; Common iipidomic becomes Ganglioside, GD3 0.6% and Ganglioside GM3 0.5%; And common fatty acid consists of myristic acid (14:0) 5.6%, Palmic acid (16:0) 18.4%, palmitoleic acid (16:1) 1.2%, heptadecanoic acid (17:0) 0.5%, stearic acid (18:0) 14.9%, oleic acid (18:1) 31.0%, linoleic acid (18:2) 3.8%, linolenic acid (18:3) 1.5% and arachidonic acid (20:4) 0.5%.

Ganglioside G600 ^TMGanglioside partly is spray-dired newborn ganglioside concentrate, has wherein added lactose to improve powder flowbility.G600 ^TMCommon lipid 30.0%, moisture 3.5%, ash 8.3% and the lactose 58.0% of consisting of of ganglioside part; Common iipidomic becomes Ganglioside, GD3 1.4%, Ganglioside GM3 0.3%, Phosphatidylserine 4.5%, phosphatidylcholine 5.1%, PHOSPHATIDYL ETHANOLAMINE 2.0% and sphingomyelins 1.7%; And common fatty acid consists of myristic acid (14:0) 4.7%, Palmic acid (16:0) 16.4%, palmitoleic acid (16:1) 1.2%, heptadecanoic acid (17:0) 0.5%, stearic acid (18:0) 17.0%, oleic acid (18:1) 33.4%, linoleic acid (18:2) 4.2%, linolenic acid (18:3) 1.4% and arachidonic acid (20:4) 0.6%.

The lipid hydrolysis thing

Realize partly-hydrolysed by the potassium hydroxide (1.5% alcoholic solution) that in the sample of 200mg lipid preparation, adds 800 μ l.The solution of gained was mixed 10 minutes, and to be neutralized to pH value with hydrochloric acid (10%) be 7.Then this solution is done (flush dry) in the nitrogen undershoot.

Cell culture, virus breeding and mensuration material

All cell culture materials are all available from Invitrogen.Rotavirus strain Wa (people) is that the John Taylor of University of Auckland (Auckland University) gives.The HT29 cell is available from ATCC (HTB-38).Monosialoganglioside GM3 cat#1503 and two ganglioside sialic acid GD3 cat#1504 are available from Matreya (Pleasant Gap, PA, USA).

The rotavirus breeding

Contain the tryptic Dulbecco MEM of 1 μ g/ml (Dulbecco ' sminimal essential medium) (DMEM) in the presence of, HT29 cell line is used for breeding Human reoviruslike agent strain Wa (neuraminidase resistance), this culture media supplemented 10% hyclone and penicillin/streptomycin (100 μ g/ml/100 units/ml).Gather in the crops rotavirus by twice freeze thawing, should virus centrifugal to remove cell debris and to be stored in-80 ℃ under 750g.Rotavirus is measured, found that it contains 1 * 106 plaque forming unit (pfu)/ml.

Rotavirus infection is measured

Used infection is measured and is based on many disclosed mensuration (Scott et al 1979; Smith et al1979; Guarino et al 1996; Superti et al 2001).To be grown in the fusion HT29 cell washed twice in aseptic PBS among the DMEM (in 96 orifice plates, inoculating with 3 * 105/ml).In plate, in the DMEM of 50 μ l volumes, carry out the double dilution of each product of wanting examination (initial concentration 5mg/ml).Except only having the contrast of cell, in all holes, add virus (104pfu/ hole), then under 37 ℃, plate was hatched two hours in the CO2 5%.Other contrast comprises that virus adds cell, only lipid, pure GM3 and pure GD3 arranged.After hatching two hours, add trypsin to all hole, this hole is contained the virus of 2 μ g/ml concentration-this step VP4 is cut into polypeptide VP8 and VP5, and it is necessary to be that virion invades in the cell.Hatching seven days among plate is lower at 37 ℃ and the CO2 5%, and checking CPE in the virulent control wells only every day.Remove culture medium, plate is washed in aseptic PBS, air-dry and fix one minute with methanol.Plate is air-dry, then use 1% crystal violet (351884W, BDH, England) in 100 μ l/ holes to dye five minutes.Plate is washed four times to remove unnecessary stain with sterilized water.The acetic acid that adds every hole 100 μ l dissolves stain, and in Biorad ELISA microwell plate detector (plate reader), reads absorbance under the wavelength of 595nm.Independently measure each sample in the situation at minimum three, and calculate the not percentage rate of infected cell.

Statistics

Utilize non-matching Student t check (for Macintosh, use be InStat) to carry out statistical analysis, thereby under the minimum dilution of product, the effect that will stem from the lipid products of Lac Bovis seu Bubali compare with virulent contrast only.

Embodiment 1-milk lipid suppresses external rotavirus infection

The ability of the rotavirus infection of the prevention cell of 16 kinds of lipid test materials of examination.Lipid test material or contrast material are nontoxic to the HT29 cell.Ganglioside, GD3 and GM3 all show activity (table 8) in concentration range.In 16 kinds of lipid test materials, 14 kinds of activity (table 9) that show the viral infection of prevention cell in concentration range are arranged.

Table 8: in the presence of the GD3 of various concentration and GM3, not by the percentage rate of the HT29 cell of rotavirus infection

Figure DEST_PATH_RE-GSB00000560341400021

^*Compare with virulent contrast only, p＜0.01 is o'clock remarkable; ^*P＜0.005 is o'clock remarkable; ^{* *}P＜0.001 is o'clock remarkable; There is not the sample of p value and only virulent contrast is significantly not different.The ND=undetermined.

Table 9: in the presence of the various Lac Bovis seu Bubali lipid parts of various concentration, not by the percentage rate of the HT29 cell of rotavirus infection

Figure DEST_PATH_RE-GSB00000560341400022

^*Compare with virulent contrast only, p＜0.01 is o'clock remarkable; ^*P＜0.005 is o'clock remarkable; ^{* *}P＜0.001 is o'clock remarkable;

There is not the sample of p value and only virulent contrast is significantly not different.

P was less than 0.001 o'clock, and concentration is five kinds of obvious Reducing the rate of infections of test material (table 9) of 0.3125mg/ml.These test materials are butterfat, β serum, the PC700 that is rich in CLA ^TMPhospholipid moiety and ganglioside part.P was less than 0.005 o'clock, and concentration is four kinds of obvious Reducing the rate of infections of test material of 0.3125mg/ml.These test materials are AMF, soft butterfat part (SSS), and PC500 ^TMAnd PC600 ^TMPhospholipid moiety.P was less than 0.01 o'clock, and concentration is three kinds of obvious Reducing the rate of infections of test material of 0.3125mg/ml.These test materials are other SH and SSH butterfat part, and the ganglioside part of hydrolysis.Remaining product is significantly not different from virus control.When concentration was low to moderate 31.25 μ g/ml, the purification of samples Cell protection of GM3 and GD3 was avoided viral infection and (is respectively 43+/-10% and 40+/-3%; P＜0.005).On ganglioside-concentrated basis, at minimum G600 ^TMUnder the concentration, G600 ^TMEffective 10 times than pure GD3 of parts.

The diarrhoea that caused by rotavirus infection can be treated or prevent to embodiment 2-milk lipid

Young rat (baby rat) animal model that is used for the Human reoviruslike agent infection can be used in and renders a service (for example, referring to Ciarlet et al 2006) in the body of determining product.

With the volume of 100 μ l, by sending the mode of entrance cavity, be that four kinds of different lipid test materials of 3g/kg body weight are fed five the largest rat sons to ten every group with concentration.All other feedings all come from lactescent female rat (mother rat).At first day and second day, the Human reoviruslike agent strain Wa (morning and evening) that feeds to rat son 100 μ l dosage for twice.To negative control rat injection (inoculate) 100 μ l phosphate buffered saline(PBS) (PBS), but need not virus infect.The positive control rat is injected 100 μ l PBS, infect with virus subsequently.Experiment was carried out 10 days after the injection rotavirus.This experiment repeats.

In order to measure infection rate, rat is weighed every day.Independent fecal specimens is collected in the preweighted vessel, and determining of once suffering from diarrhoea every day.According to stool colour, denseness and amount, every day diarrhoea is carried out following 1 to 4 marking.

1. normal feces-normal color (brown) and denseness.

2. slight diarrhoea-unusual color (green or yellow green) but normal denseness.

3. moderate diarrhoea-normal color (brown) but watery denseness.

4. severe diarrhea-unusual color and watery denseness.

Faecal samples is processed into 10% solution among cold (4 ℃) PBS, this solution contains penicillin (200U/ml), streptomycin (200 μ l/ml) and gentamycin (2mg/ml), and as indicated above in cell culture with the five equilibrium replication of 10 μ l to determine the level of infective rotavirus.In external test, these levels represent the not percentage rate of infected cell: not infected cell %=(OD of specimen) * 100/ (OD of negative control), wherein OD is the optical density of solution in the hole.

Table 10: the seriousness of the rat diarrhoea of the butterfat of the high CLA of feeding

Figure DEST_PATH_RE-GSB00000560341400041

Table 11: feeding G600 ^TMThe seriousness of the rat diarrhoea of butterfat

Figure DEST_PATH_RE-GSB00000560341400042

Table 12: the seriousness of the rat diarrhoea of feeding β serum part

In measuring, external rotavirus measures faecal samples to determine the not percentage rate of infected cell.For the rat (Figure 1A) of the butterfat of the high CLA of feeding, process and infected contrast between difference be significant in first day (P＜0.001), the 3rd day (P＜0.025), the 7th day (P＜0.05) and the 8th day (P＜0.025).For feeding G600 ^TMThe rat (Figure 1B) of part, process and infected contrast between difference in the 3rd day (P＜0.001), the 4th day (P＜0.001), the 6th day (P=0.001), the 7th day (P＜0.001) and the 8th day (P＜0.001) is significant.

Commercial Application

The present invention has practicality in treatment or prevention rotavirus infection.Can be with described compositions as food, beverage, food additive, beverage additive, supplementary, nutriment, medicated food, health product, medicine (medicament) or medicine (pharmaceutical).

What it will be appreciated by those skilled in the art that is only provide foregoing description by exemplary illustration, and the present invention not to be limited by these exemplary illustrations.

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Claims

1. the purposes in the compositions of rotavirus infection of one or more butter fat compositionss neuraminidase resistance in for the preparation for the treatment of or prevention individuality, described one or more butter fat compositionss are selected from:

(i). butterfat, one or more butterfat part or above-mentioned combinations,

(ii). anhydrous milkfat, one or more anhydrous milkfats part or above-mentioned any two or more combination,

(iii). one or more are rich in the part of the butterfat of phospholipid, and it contains 5%w/w to 100%w/w lipid and 5%w/w to 85%w/w phospholipid,

(iv). one or more are rich in the part of the butterfat of ganglioside, and it contains 5%w/w to 100%w/w lipid and 5%w/w to 85%w/w phospholipid,

(v). (i) any one or one or more multiple hydrolysates in (iv), and

(vi). (i) the arbitrarily combination of two or more in (v).

2. purposes as claimed in claim 1, wherein said rotavirus is Human reoviruslike agent.

3. purposes as claimed in claim 1 or 2, wherein said individuality is the people.

4. purposes as claimed in claim 1 or 2, wherein said individuality is child or baby.

5. purposes as claimed in claim 1 or 2, wherein said individuality is the child of immunocompromised host or the baby of immunocompromised host.

6. purposes as claimed in claim 1 or 2, wherein said individuality is the adult.

7. purposes as claimed in claim 1 or 2, wherein said individuality is for surpassing 55 years old adult.

8. purposes as claimed in claim 1 or 2, wherein said individuality is the adult of immunocompromised host.

9. purposes as claimed in claim 1 or 2, wherein said individuality are 55 years old the adult of surpassing of immunocompromised host.

10. such as the described purposes of arbitrary claim in the claim 1 to 9, be used for the treatment of or prevent the rotavirus infection of diarrhea inducing.

11. such as the described purposes of arbitrary claim in the claim 1 to 9, the diarrhoea that is used for the treatment of or prevents to be caused by rotavirus infection.

12. such as the described purposes of arbitrary claim in the claim 1 to 11, wherein said butterfat comprises 5% to 100% lipid.

13. such as the described purposes of arbitrary claim in the claim 1 to 12, wherein said butterfat comprises 40% to 100% lipid.

14. such as the described purposes of arbitrary claim in the claim 1 to 13, comprise and use anhydrous butter fat, one or more anhydrous milkfat part or above-mentioned combinations, to be used for treating or preventing individual rotavirus infection.

15. such as the described purposes of arbitrary claim in the claim 1 to 14, wherein said anhydrous milkfat partly is selected from one or more hard butterfat parts, one or more soft butterfat parts and above-mentioned any two or more combination in any.

16. such as the described purposes of arbitrary claim in the claim 1 to 14, wherein said anhydrous milkfat partly is selected from combination and above-mentioned any two or more combination in any of the combination of the combination of hard butterfat part, soft butterfat part, hard butterfat part and soft butterfat part.

17. such as the described purposes of arbitrary claim among the claim 1-16, wherein said anhydrous milkfat comprises 98% to 100% butterfat.

18. such as the described purposes of arbitrary claim in the claim 1 to 13, comprise and use one or more to be rich in part or the part of one or more butter fats that are rich in ganglioside or the above-mentioned combination of the butter fat of phospholipid, to be used for the treatment of or to prevent the rotavirus infection of individuality.

19. such as the described purposes of arbitrary claim in claim 1 to 13 and 18, the wherein said part that is rich in phospholipid is selected from buttermilk, one or more buttermilk parts, butter serum, one or more butter serum parts, β serum, one or more β serum parts, one or more sphingolipid parts, one or more butterfat ball membrane lipid parts, one or more phospholipid moieties, one or more complex lipids parts and above-mentioned any two or more combination in any.

20. such as the described purposes of arbitrary claim in claim 1 to 13 and 18, the wherein said part that is rich in ganglioside is selected from buttermilk, one or more buttermilk parts, butter serum, one or more butter serum parts, β serum, one or more β serums parts, one or more are rich in part and above-mentioned any two or more combination in any of part, one or more β serums that are rich in GD3 and GM3 of the part of the β serum of GD3, β serum that one or more are rich in GM3.

21. such as the described purposes of arbitrary claim in the claim 1 to 20, wherein said part comprises

(a) protein of the lipid of 5%w/w to 95%w/w and 0%w/w to 75%w/w, or

(b) protein of the lipid of 15%w/w to 95%w/w and 0%w/w to 75%w/w, or

(c) ganglioside of the phospholipid of the protein of the lipid of 5%w/w to 95%w/w, 0%w/w to 75%w/w, 5%w/w to 85%w/w and 0%w/w to 5%w/w, or

(d) ganglioside of the phospholipid of the protein of the lipid of 15%w/w to 95%w/w, 0%w/w to 65%w/w, 5%w/w to 70%w/w and 0%w/w to 2.5%w/w.

22. such as the described purposes of arbitrary claim in the claim 1 to 20, wherein said part comprises

(a) the MFGM albumen of the phospholipid of the lipid of the protein of 25%w/w to 35%w/w, 12%w/w to 25%w/w, 5%w/w to 15%w/w, 5%w/w to 15%w/w and the ganglioside of 0.2%w/w to 0.9%w/w, or

(b) the MFGM albumen of the phospholipid of the lipid of the protein of 40%w/w to 60%w/w, 25%w/w to 45%w/w, 10%w/w to 25%w/w, 5%w/w to 20%w/w and the ganglioside of 0.5%w/w to 2.0%w/w, or

(c) the MFGM albumen of the Phosphatidylserine of the sphingomyelins of the PHOSPHATIDYL ETHANOLAMINE of the phosphatidylcholine of the phospholipid of the lipid of the protein of 50%w/w to 70%w/w, 12%w/w to 32%w/w, 5%w/w to 25%w/w, 2%w/w to 8%w/w, 2%w/w to 10%w/w, 2%w/w to 8%w/w and 1%w/w to 3%w/w, 10%w/w to 20%w/w and the ganglioside of 0.5%w/w to 2.5%w/w, or

(d) lipid of the protein of 0%w/w to 10%w/w, 85%w/w to 97%w/w, 25% to 35%w/w phospholipid, the phosphatidylcholine of 5%w/w to 10%w/w, the PHOSPHATIDYL ETHANOLAMINE of 7%w/w to 13%w/w, the sphingomyelins of 4%w/w to 9%w/w, the Phosphatidylserine of 2%w/w to 5%w/w, the phosphatidylinositols of 1%w/w to 3%w/w, the MFGM albumen of 0%w/w to 5%w/w and the ganglioside of 1%w/w to 3%w/w, or

(e) the MFGM albumen of the phosphatidylinositols of the Phosphatidylserine of the sphingomyelins of the PHOSPHATIDYL ETHANOLAMINE of the phosphatidylcholine of the phospholipid of the lipid of the protein of 10%w/w to 15%w/w, 80%w/w to 95%w/w, 60%w/w to 80%w/w, 10%w/w to 20%w/w, 18%w/w to 28%w/w, 10%w/w to 20%w/w, 4%w/w to 12%w/w, 2%w/w to 10%w/w, 0%w/w to 5%w/w and the ganglioside of 1%w/w to 5%w/w, or

(f) phosphatidylinositols of the Phosphatidylserine of the sphingomyelins of the PHOSPHATIDYL ETHANOLAMINE of the phosphatidylcholine of the phospholipid of the lipid of 75%w/w to 99%w/w, 15%w/w to 35%w/w, 5%w/w to 15%w/w, 5%w/w to 15%w/w, 4%w/w to 15%w/w, 0.1%w/w to 2%w/w and 0.1%w/w to 2%w/w, or

(g) phosphatidylinositols of the Phosphatidylserine of the sphingomyelins of the PHOSPHATIDYL ETHANOLAMINE of the phosphatidylcholine of the phospholipid of the lipid of 75%w/w to 95%w/w, 50%w/w to 90%w/w, 10%w/w to 45%w/w, 12%w/w to 25%w/w, 12%w/w to 25%w/w, 1%w/w to 6%w/w and 0.5%w/w to 4%w/w, or

(h) Phosphatidylserine of the sphingomyelins of the PHOSPHATIDYL ETHANOLAMINE of the phosphatidylcholine of the phospholipid of the lipid of 80%w/w to 90%w/w, 65%w/w to 75%w/w, 10%w/w to 30%w/w, 12%w/w to 22%w/w, 12%w/w to 22%w/w and 1%w/w to 3%w/w, or

(i) ganglioside of the pure and mild 0.2%w/w to 1%w/w of phosphatidyl-4 of the Phosphatidylserine of the sphingomyelins of the PHOSPHATIDYL ETHANOLAMINE of the phosphatidylcholine of the lipid of 25%w/w to 45%w/w, 10%w/w to 30%w/w phospholipid, 2%w/w to 5%w/w, 3%w/w to 7%w/w, 2%w/w to 5%w/w, 2%w/w to 12%w/w, 1%w/w to 5%w/w, or

(j) ganglioside of the pure and mild 0.8%w/w to 3.5%w/w of phosphatidyl-4 of the Phosphatidylserine of the sphingomyelins of the PHOSPHATIDYL ETHANOLAMINE of the lipid of 20%w/w to 40%w/w, 5%w/w to 30%w/w phospholipid, 1%w/w to 5%w/w phosphatidylcholine, 2%w/w to 8%w/w, 0.5%w/w to 5%w/w, 1%w/w to 10%w/w, 1%w/w to 6%w/w.

23. such as the described purposes of arbitrary claim in the claim 1 to 22, wherein said compositions also comprises lactoferrin, functional Lactoferrtin variants, functional lactoferrin fragment or above-mentioned any two or more combination.

24. such as the described purposes of arbitrary claim in the claim 1 to 22, wherein said compositions also comprises ferrum-lactoferrin, functional ferrum-Lactoferrtin variants, functional ferrum-lactoferrin fragment or above-mentioned any two or more combination.

25. such as the described purposes of arbitrary claim in the claim 1 to 24, wherein described compositions is mixed with infant formula.

26. such as the described purposes of arbitrary claim in the claim 1 to 24, wherein described compositions is mixed with larger infant formula or growth milk replacer.